2,006 results match your criteria Neuronal Ceroid Lipofuscinoses


Validity of a rapid and simple fluorometric tripeptidyl peptidase 1 (TPP1) assay using dried blood specimens to diagnose CLN2 disease.

Clin Chim Acta 2019 Feb 13;492:69-71. Epub 2019 Feb 13.

Metabolic Laboratory, Center of Diagnostics, Hamburg, Germany; NCL Clinic, Department of Pediatrics, University Medical Center Eppendorf, Hamburg, Germany. Electronic address:

Purpose: CLN2 disease is a genetic disorder caused by dysfunction of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1) that belongs to the neuronal ceroid lipofuscinoses (NCL) and leads to epilepsy, dementia, and death in young persons. CLN2 disease has recently become treatable by enzyme replacement, which can only be effective when the disease is diagnosed early. We have investigated the reliability of a test for TPP1 deficiency in dried blood specimens (DBS) to detect CLN2 disease. Read More

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http://dx.doi.org/10.1016/j.cca.2019.02.010DOI Listing
February 2019

Considerations in multi-gene panel testing in pediatric ophthalmology.

J AAPOS 2019 Feb 12. Epub 2019 Feb 12.

National Eye Institute, National Institutes of Health, Bethesda, MD, 20892. Electronic address:

Multi-gene panel testing is used increasingly in ophthalmology practice as an efficient and cost-effective method for diagnosing inherited eye conditions. Panel testing is a powerful diagnostic tool, and it has the potential to reveal syndromic information in patients with seemingly isolated eye findings. This case series highlights our experience with 4 children in 3 families who were referred for evaluation of an isolated retinal degeneration and diagnosed with neuronal ceroid lipofuscinosis on panel testing. Read More

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http://dx.doi.org/10.1016/j.jaapos.2019.01.008DOI Listing
February 2019

Lysosomal storage disease overview.

Authors:
Angela Sun

Ann Transl Med 2018 Dec;6(24):476

Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.

The lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders that are caused for the most part by enzyme deficiencies within the lysosome resulting in accumulation of undegraded substrate. This storage process leads to a broad spectrum of clinical manifestations depending on the specific substrate and site of accumulation. Examples of LSDs include the mucopolysaccharidoses, mucolipidoses, oligosaccharidoses, Pompe disease, Gaucher disease, Fabry disease, the Niemann-Pick disorders, and neuronal ceroid lipofuscinoses. Read More

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http://dx.doi.org/10.21037/atm.2018.11.39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331358PMC
December 2018
1 Read

Recent Insights into NCL Protein Function Using the Model Organism .

Cells 2019 Feb 2;8(2). Epub 2019 Feb 2.

Department of Biology, Trent University, 1600 West Bank Drive, Peterborough, ON K9L 0G2, Canada.

The neuronal ceroid lipofuscinoses (NCLs) are a group of devastating neurological disorders that have a global distribution and affect people of all ages. Commonly known as Batten disease, this form of neurodegeneration is linked to mutations in 13 genetically distinct genes. The precise mechanisms underlying the disease are unknown, in large part due to our poor understanding of the functions of NCL proteins. Read More

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http://dx.doi.org/10.3390/cells8020115DOI Listing
February 2019

Tracking sex-dependent differences in a mouse model of CLN6-Batten disease.

Orphanet J Rare Dis 2019 Jan 21;14(1):19. Epub 2019 Jan 21.

Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, SD, USA.

Background: CLN6-Batten disease is a rare neurodevelopmental disorder characterized pathologically by the accumulation of lysosomal storage material, glial activation and neurodegeneration, and phenotypically by loss of vision, motor coordination, and cognitive ability, with premature death occurring in the second decade of life. In this study, we investigate whether sex differences in a mouse model of CLN6-Batten disease impact disease onset and progression.

Results: A number of noteworthy differences were observed including elevated accumulation of mitochondrial ATP synthase subunit C in the thalamus and cortex of female Cln6 mutant mice at 2 months of age. Read More

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http://dx.doi.org/10.1186/s13023-019-0994-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341540PMC
January 2019

Autophagy-lysosome pathway alterations and alpha-synuclein up-regulation in the subtype of neuronal ceroid lipofuscinosis, CLN5 disease.

Sci Rep 2019 Jan 17;9(1):151. Epub 2019 Jan 17.

Division of Biology, Kansas State University, Manhattan, KS, 66506, USA.

Neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative lysosomal storage disorders. CLN5 deficiency causes a subtype of NCL, referred to as CLN5 disease. CLN5 is a soluble lysosomal protein with an unclear function in the cell. Read More

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http://dx.doi.org/10.1038/s41598-018-36379-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336884PMC
January 2019

Emerging new roles of the lysosome and neuronal ceroid lipofuscinoses.

Mol Neurodegener 2019 01 16;14(1). Epub 2019 Jan 16.

Section on Developmental Genetics, Program on Endocrinology and Molecular Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, The National Institutes of Health, Bethesda, Maryland, 20892-1830, USA.

Neuronal Ceroid Lipofuscinoses (NCLs), commonly known as Batten disease, constitute a group of the most prevalent neurodegenerative lysosomal storage disorders (LSDs). Mutations in at least 13 different genes (called CLNs) cause various forms of NCLs. Clinically, the NCLs manifest early impairment of vision, progressive decline in cognitive and motor functions, seizures and a shortened lifespan. Read More

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https://molecularneurodegeneration.biomedcentral.com/article
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http://dx.doi.org/10.1186/s13024-018-0300-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335712PMC
January 2019
3 Reads

Batten disease: biochemical and molecular characterization revealing novel PPT1 and TPP1 gene mutations in Indian patients.

BMC Neurol 2018 Dec 12;18(1):203. Epub 2018 Dec 12.

FRIGE's Institute of Human Genetics, FRIGE House, Jodhpur Gam Road, Satellite, Ahmedabad, Gujarat, 380015, India.

Background: Neuronal ceroid lipofuscinoses type I and type II (NCL1 and NCL2) also known as Batten disease are the commonly observed neurodegenerative lysosomal storage disorder caused by mutations in the PPT1 and TPP1 genes respectively. Till date, nearly 76 mutations in PPT1 and approximately 140 mutations, including large deletion/duplications, in TPP1 genes have been reported in the literature. The present study includes 34 unrelated Indian patients (12 females and 22 males) having epilepsy, visual impairment, cerebral atrophy, and cerebellar atrophy. Read More

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http://dx.doi.org/10.1186/s12883-018-1206-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292089PMC
December 2018
3 Reads

Autophagic vacuolar myopathy is a common feature of CLN3 disease.

Ann Clin Transl Neurol 2018 Nov 14;5(11):1385-1393. Epub 2018 Oct 14.

Department of Neuropathology Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health Berlin Germany.

Objective: The neuronal ceroid lipofuscinoses (NCL) are genetic degenerative disorders of brain and retina. NCL with juvenile onset (JNCL) is genetically heterogeneous but most frequently caused by mutations of CLN3. Classical juvenile CLN3 includes a rare protracted form, which has previously been linked to autophagic vacuolar myopathy (AVM). Read More

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http://doi.wiley.com/10.1002/acn3.662
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http://dx.doi.org/10.1002/acn3.662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243389PMC
November 2018
11 Reads

Clinical challenges and future therapeutic approaches for neuronal ceroid lipofuscinosis.

Lancet Neurol 2019 Jan 21;18(1):107-116. Epub 2018 Nov 21.

UCL Institute of Ophthalmology, University College London, London, UK.

Treatment of the neuronal ceroid lipofuscinoses, also known as Batten disease, is at the start of a new era because of diagnostic and therapeutic advances relevant to this group of inherited neurodegenerative and life-limiting disorders that affect children. Diagnosis has improved with the use of comprehensive DNA-based tests that simultaneously screen for many genes. The identification of disease-causing mutations in 13 genes provides a basis for understanding the molecular mechanisms underlying neuronal ceroid lipofuscinoses, and for the development of targeted therapies. Read More

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http://dx.doi.org/10.1016/S1474-4422(18)30368-5DOI Listing
January 2019
11 Reads

Neuronal ceroid lipofuscinosis related ER membrane protein CLN8 regulates PP2A activity and ceramide levels.

Biochim Biophys Acta Mol Basis Dis 2019 Feb 16;1865(2):322-328. Epub 2018 Nov 16.

Division of Biology, Kansas State University, Manhattan, KS 66506, USA; Graduate Biochemistry Group, Kansas State University, Manhattan, Kansas 66506, USA. Electronic address:

The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative lysosomal storage disorders. CLN8 deficiency causes a subtype of NCL, referred to as CLN8 disease. CLN8 is an ER resident protein with unknown function; however, a role in ceramide metabolism has been suggested. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09254439183047
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http://dx.doi.org/10.1016/j.bbadis.2018.11.011DOI Listing
February 2019
6 Reads

Neuronal Ceroid Lipofuscinoses: Connecting Calcium Signalling through Calmodulin.

Cells 2018 Oct 29;7(11). Epub 2018 Oct 29.

Department of Biology, Trent University, Peterborough, ON K9L 0G2, Canada.

Despite the increased focus on the role of calcium in the neuronal ceroid lipofuscinoses (NCLs, also known as Batten disease), links between calcium signalling and the proteins associated with the disease remain to be identified. A central protein in calcium signalling is calmodulin (CaM), which regulates many of the same cellular processes affected in the NCLs. In this study, we show that 11 of the 13 NCL proteins contain putative CaM-binding domains (CaMBDs). Read More

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http://dx.doi.org/10.3390/cells7110188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262527PMC
October 2018
3 Reads

Cln3 function is linked to osmoregulation in a Dictyostelium model of Batten disease.

Biochim Biophys Acta Mol Basis Dis 2018 11 11;1864(11):3559-3573. Epub 2018 Aug 11.

Department of Biology, Trent University, Peterborough, Ontario, Canada. Electronic address:

Mutations in CLN3 cause a juvenile form of neuronal ceroid lipofuscinosis (NCL), commonly known as Batten disease. Currently, there is no cure for NCL and the mechanisms underlying the disease are not well understood. In the social amoeba Dictyostelium discoideum, the CLN3 homolog, Cln3, localizes predominantly to the contractile vacuole (CV) system. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09254439183029
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http://dx.doi.org/10.1016/j.bbadis.2018.08.013DOI Listing
November 2018
1 Read

Flupirtine derivatives as potential treatment for the neuronal ceroid lipofuscinoses.

Ann Clin Transl Neurol 2018 Sep 14;5(9):1089-1103. Epub 2018 Aug 14.

Department of Biochemistry and Molecular Genetics American University of Beirut Medical Center Beirut Lebanon.

Objective: Neuronal Ceroid Lipofuscinoses (NCL) are fatal inherited neurodegenerative diseases with established neuronal cell death and increased ceramide levels in brain, hence, a need for disease-modifying drug candidates, with potential to enhance growth, reduce apoptosis and lower ceramide in neuronal precursor PC12 cells and human NCL cell lines using enhanced flupirtine aromatic carbamate derivatives in vitro.

Methods: Aromatic carbamate derivatives were tested by establishing growth curves under pro-apoptotic conditions and activity evaluated by trypan blue and JC-1 staining, as well as a drop in pro-apoptotic ceramide in neuronal precursor PC12 cells following siRNA knockdown of the gene, and CLN1-/CLN2-/CLN3-/CLN6-/CLN8 patient-derived lymphoblasts. Ceramide levels were determined in CLN1-/CLN2-/CLN3-/CLN6-/CLN8 patient-derived lymphoblasts before and after treatment. Read More

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http://dx.doi.org/10.1002/acn3.625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144451PMC
September 2018
16 Reads

Novel in-frame deletion in MFSD8 gene revealed by trio whole exome sequencing in an Iranian affected with neuronal ceroid lipofuscinosis type 7: a case report.

J Med Case Rep 2018 Sep 25;12(1):281. Epub 2018 Sep 25.

Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Background: The neuronal ceroid lipofuscinoses are a group of neurodegenerative, lysosomal storage disorders. They are inherited as an autosomal recessive pattern with the exception of adult neuronal ceroid lipofuscinosis, which can be inherited in either an autosomal recessive or an autosomal dominant manner. The neuronal ceroid lipofuscinoses are characterized by accumulation of autofluorescent lipopigments in the cells and one of the most important pathological manifestations is ceroid accumulation in the lysosomes. Read More

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http://dx.doi.org/10.1186/s13256-018-1788-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154911PMC
September 2018

Early lysosomal maturation deficits in microglia triggers enhanced lysosomal activity in other brain cells of progranulin knockout mice.

Mol Neurodegener 2018 09 4;13(1):48. Epub 2018 Sep 4.

Chair of Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig-Maximilians-Universität München, 81377, Munich, Germany.

Background: Heterozygous loss-of-function mutations in the progranulin gene (GRN) lead to frontotemporal lobar degeneration (FTLD) while the complete loss of progranulin (PGRN) function results in neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. Thus the growth factor-like protein PGRN may play an important role in lysosomal degradation. In line with a potential lysosomal function, PGRN is partially localized and processed in lysosomes. Read More

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http://dx.doi.org/10.1186/s13024-018-0281-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6123925PMC
September 2018
1 Read

A novel MFSD8 mutation in a Russian patient with neuronal ceroid lipofuscinosis type 7: a case report.

BMC Med Genet 2018 Aug 25;19(1):151. Epub 2018 Aug 25.

Institute of Biomedical Chemistry, Pogodinskaya street 10 building 8, 119121, Moscow, Russia.

Background: Neuronal ceroid lipofuscinoses (NCLs) are the most common autosomal recessive neurodegenerative disorders in children. Clinical manifestations include progressive cognitive decline, motor impairment, ataxia, visual loss, seizures and early death. To date more than 440 NCL-causing mutations in 13 genes are known. Read More

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http://dx.doi.org/10.1186/s12881-018-0669-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109285PMC
August 2018
12 Reads

Computed tomography provides enhanced techniques for longitudinal monitoring of progressive intracranial volume loss associated with regional neurodegeneration in ovine neuronal ceroid lipofuscinoses.

Brain Behav 2018 Sep 23;8(9):e01096. Epub 2018 Aug 23.

Faculty of Agriculture and Life Sciences, Lincoln University, Lincoln, New Zealand.

Introduction: The neuronal ceroid lipofuscinoses (NCLs; Batten disease) are a group of fatal neurodegenerative lysosomal storage diseases of children caused by various mutations in a range of genes. Forms associated with mutations in two of these, CLN5 and CLN6, are being investigated in well-established sheep models. Brain atrophy leading to psychomotor degeneration is among the defining features, as is regional progressive ossification of the inner cranium. Read More

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http://dx.doi.org/10.1002/brb3.1096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160654PMC
September 2018
13 Reads

Compromised astrocyte function and survival negatively impact neurons in infantile neuronal ceroid lipofuscinosis.

Acta Neuropathol Commun 2018 Aug 8;6(1):74. Epub 2018 Aug 8.

Department of Basic and Clinical Neuroscience, King's College London, Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute, 5 Cutcombe Road, London, SE5 9RX, UK.

The neuronal ceroid lipofuscinoses (NCLs) are the most common cause of childhood dementia and are invariably fatal. Early localized glial activation occurs in these disorders, and accurately predicts where neuronal loss is most pronounced. Recent evidence suggests that glial dysfunction may contribute to neuron loss, and we have now explored this possibility in infantile NCL (INCL, CLN1 disease). Read More

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http://dx.doi.org/10.1186/s40478-018-0575-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081811PMC

Searching for novel biomarkers using a mouse model of CLN3-Batten disease.

PLoS One 2018 7;13(8):e0201470. Epub 2018 Aug 7.

Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, South Dakota, United States of America.

CLN3-Batten disease is a rare, autosomal recessive disorder involving seizures, visual, motor and cognitive decline, and premature death. The Cln3Δex7/8 mouse model recapitulates several phenotypic characteristics of the most common 1.02kb disease-associated deletion. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0201470PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6080763PMC
January 2019
2 Reads

Longitudinal In Vivo Monitoring of the CNS Demonstrates the Efficacy of Gene Therapy in a Sheep Model of CLN5 Batten Disease.

Mol Ther 2018 Oct 17;26(10):2366-2378. Epub 2018 Jul 17.

Department of Molecular Biosciences, Faculty of Agriculture and Life Sciences, Lincoln University, Lincoln 7647, New Zealand; Department of Radiology, University of Otago, Christchurch 8140, New Zealand. Electronic address:

Neuronal ceroid lipofuscinoses (NCLs; Batten disease) are neurodegenerative lysosomal storage diseases predominantly affecting children. Single administration of brain-directed lentiviral or recombinant single-stranded adeno-associated virus 9 (ssAAV9) vectors expressing ovine CLN5 into six pre-clinically affected sheep with a naturally occurring CLN5 NCL resulted in long-term disease attenuation. Treatment efficacy was demonstrated by non-invasive longitudinal in vivo monitoring developed to align with assessments used in human medicine. Read More

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http://dx.doi.org/10.1016/j.ymthe.2018.07.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171082PMC
October 2018
6 Reads

[Clinical features and genetics studies of Finnish variant late infantile neuronal ceroid lipofuscinosis in two families].

Zhonghua Er Ke Za Zhi 2018 Aug;56(8):601-604

Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou 510623, China.

To report clinical feature and results of genetic analysis of 3 patients from 2 families with Finnish variant late infantile neuronal ceroid lipofuscinosis. The clinical and ultrastructural features of 3 patients with progressive neurodegenerative diseases were retrospectively analyzed from October 2014 to December 2016 in Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center. The whole exon sequencing and Sanger sequencing were used to analyze the molecular genetics of the patients and their parents. Read More

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http://dx.doi.org/10.3760/cma.j.issn.0578-1310.2018.08.009DOI Listing
August 2018
3 Reads

First case of genetically confirmed CLN3 disease in Chinese with cDNA sequencing revealing pathogenicity of a novel splice site variant.

Clin Chim Acta 2018 Nov 24;486:151-155. Epub 2018 Jul 24.

Kowloon West Cluster Laboratory Genetic Service, Chemical Pathology Laboratory, Department of Pathology, Princess Margaret Hospital, Hong Kong. Electronic address:

Background: Juvenile neuronal ceroid lipofuscinosis (CLN3 disease) is a hereditary progressive neurodegenerative disease well documented among Caucasians, but such clinical data and genetic characterization is lacking among Asian populations.

Patient And Methods: A 13-year-old Chinese girl presented for diagnostic evaluation with retinitis pigmentosa, generalised tonic-clonic seizure and cerebellar ataxia. Electron microscopy of whole blood and skin biopsy, and mutation analysis of CLN3 gene with genomic DNA and cDNA, were performed. Read More

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http://dx.doi.org/10.1016/j.cca.2018.07.040DOI Listing
November 2018
8 Reads

Secretion and function of Cln5 during the early stages of Dictyostelium development.

Biochim Biophys Acta Mol Cell Res 2018 Jul 23;1865(10):1437-1450. Epub 2018 Jul 23.

Department of Biology, Trent University, Peterborough, Ontario, Canada.

Mutations in CLN5 cause neuronal ceroid lipofuscinosis (NCL), a currently untreatable neurodegenerative disorder commonly known as Batten disease. Several genetic models have been generated to study the function of CLN5, but one limitation has been the lack of a homolog in lower eukaryotic model systems. Our previous work revealed a homolog of CLN5 in the social amoeba Dictyostelium discoideum. Read More

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http://dx.doi.org/10.1016/j.bbamcr.2018.07.017DOI Listing
July 2018
7 Reads

Progress in gene and cell therapies for the neuronal ceroid lipofuscinoses.

Expert Opin Biol Ther 2018 07 2;18(7):755-764. Epub 2018 Jul 2.

a Department of Neurosurgery , Emory University , Atlanta , GA , USA.

Introduction: The neuronal ceroid lipofuscinoses (NCLs) are a subset of lysosomal storage diseases (LSDs) that cause myoclonic epilepsy, loss of cognitive and motor function, degeneration of the retina leading to blindness, and early death. Most are caused by loss-of-function mutations in either lysosomal proteins or transmembrane proteins. Current therapies are supportive in nature. Read More

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http://dx.doi.org/10.1080/14712598.2018.1492544DOI Listing
July 2018
1 Read

Altered Cerebellar Short-Term Plasticity but No Change in Postsynaptic AMPA-Type Glutamate Receptors in a Mouse Model of Juvenile Batten Disease.

eNeuro 2018 Mar-Apr;5(2). Epub 2018 May 17.

Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, United Kingdom.

Juvenile Batten disease is the most common progressive neurodegenerative disorder of childhood. It is associated with mutations in the gene, causing loss of function of CLN3 protein and degeneration of cerebellar and retinal neurons. It has been proposed that changes in granule cell AMPA-type glutamate receptors (AMPARs) contribute to the cerebellar dysfunction. Read More

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http://eneuro.org/lookup/doi/10.1523/ENEURO.0387-17.2018
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http://dx.doi.org/10.1523/ENEURO.0387-17.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956745PMC
January 2019
2 Reads

Gene Therapy Approaches to Treat the Neurodegeneration and Visual Failure in Neuronal Ceroid Lipofuscinoses.

Adv Exp Med Biol 2018 ;1074:91-99

UCL Institute of Ophthalmology, Department of Genetics & NIHR BRC at Moorfields Eye Hospital, London, UK.

Neuronal ceroid lipofuscinoses (NCLs) are a group of fatal, inherited lysosomal storage disorders mostly affecting the central nervous system of children. Symptoms include vision loss, seizures, motor deterioration and cognitive decline ultimately resulting in premature death. Studies in animal models showed that the diseases are amenable to gene supplementation therapies, and over the last decade, major advances have been made in the (pre)clinical development of these therapies. Read More

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http://dx.doi.org/10.1007/978-3-319-75402-4_12DOI Listing
January 2018
3 Reads

Study of Intraventricular Cerliponase Alfa for CLN2 Disease.

N Engl J Med 2018 05 24;378(20):1898-1907. Epub 2018 Apr 24.

From the Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (A.S., A.K.); BioMarin Pharmaceutical, Novato, CA (T.A., H.C., P.S., D.J.); the Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Rome (N.S.); Nationwide Children's Hospital and Ohio State University, Columbus (E.L.R.); UCL Great Ormond Street Institute of Child Health, London (P.G.); and the Citigroup Biomedical Imaging Center, Departments of Radiology and Genetic Medicine, Weill Cornell Medical College, New York (D.B., J.P.D.).

Background: Recombinant human tripeptidyl peptidase 1 (cerliponase alfa) is an enzyme-replacement therapy that has been developed to treat neuronal ceroid lipofuscinosis type 2 (CLN2) disease, a rare lysosomal disorder that causes progressive dementia in children.

Methods: In a multicenter, open-label study, we evaluated the effect of intraventricular infusion of cerliponase alfa every 2 weeks in children with CLN2 disease who were between the ages of 3 and 16 years. Treatment was initiated at a dose of 30 mg, 100 mg, or 300 mg; all the patients then received the 300-mg dose for at least 96 weeks. Read More

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http://dx.doi.org/10.1056/NEJMoa1712649DOI Listing
May 2018
17 Reads
3 Citations
55.870 Impact Factor

Modulating membrane fluidity corrects Batten disease phenotypes in vitro and in vivo.

Neurobiol Dis 2018 Jul 13;115:182-193. Epub 2018 Apr 13.

The Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States; Department of Pathology & Laboratory Medicine, Philadelphia, PA 19104, United States. Electronic address:

The neuronal ceroid lipofuscinoses are a class of inherited neurodegenerative diseases characterized by the accumulation of autofluorescent storage material. The most common neuronal ceroid lipofuscinosis has juvenile onset with rapid onset blindness and progressive degeneration of cognitive processes. The juvenile form is caused by mutations in the CLN3 gene, which encodes the protein CLN3. Read More

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http://dx.doi.org/10.1016/j.nbd.2018.04.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5969532PMC
July 2018
2 Reads

Occipital epilepsy versus progressive myoclonic epilepsy in a patient with continuous occipital spikes and photosensitivity in electroencephalogram: A case report.

Medicine (Baltimore) 2018 Apr;97(15):e0299

Department of Neurology and Neuroscience Center, The First Hospital of JiLin University, Changchun.

Introduction: Progressive myoclonic epilepsy (PME) is rare epilepsy syndrome. Although EEG is a useful neurophysiological technique in the evaluation of epilepsy, few EEG abnormalities have been described in PME. So, how to use EEG hints to establish the suspected diagnosis of PME as soon as possible should be addressed. Read More

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http://dx.doi.org/10.1097/MD.0000000000010299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908557PMC
April 2018
6 Reads

The Retromer Complex and Sorting Nexins in Neurodegenerative Diseases.

Front Aging Neurosci 2018 26;10:79. Epub 2018 Mar 26.

Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Collaborative Innovation Center for Brain Science, Xiamen University, Xiamen, China.

The retromer complex and associated sorting nexins (SNXs) comprise a critical trafficking machinery which mediates endosomal protein sorting. Retromer and/or SNX dysfunction has been linked to several neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and Down's syndrome (DS). In AD, deficiency of the retromer complex or its cargo proteins impairs endosomal trafficking of amyloid precursor protein (APP), resulting in the overproduction of β-amyloid (Aβ). Read More

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http://dx.doi.org/10.3389/fnagi.2018.00079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5879135PMC
March 2018
3 Reads

Neural stem cells for disease modeling and evaluation of therapeutics for infantile (CLN1/PPT1) and late infantile (CLN2/TPP1) neuronal ceroid lipofuscinoses.

Orphanet J Rare Dis 2018 Apr 10;13(1):54. Epub 2018 Apr 10.

National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Bethesda, MD, 20892, USA.

Background: Infantile and late infantile neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage diseases affecting the central nervous system (CNS). The infantile NCL (INCL) is caused by mutations in the PPT1 gene and late-infantile NCL (LINCL) is due to mutations in the TPP1 gene. Deficiency in PPT1 or TPP1 enzyme function results in lysosomal accumulation of pathological lipofuscin-like material in the patient cells. Read More

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http://dx.doi.org/10.1186/s13023-018-0798-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891977PMC
April 2018
5 Reads

Prevention of Photoreceptor Cell Loss in a Cln6 Mouse Model of Batten Disease Requires CLN6 Gene Transfer to Bipolar Cells.

Mol Ther 2018 05 2;26(5):1343-1353. Epub 2018 Mar 2.

Department of Genetics, UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK; NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, City Road, London EC1V 2PD, UK. Electronic address:

The neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage disorders characterized by general neurodegeneration and premature death. Sight loss is also a major symptom in NCLs, severely affecting the quality of life of patients, but it is not targeted effectively by brain-directed therapies. Here we set out to explore the therapeutic potential of an ocular gene therapy to treat sight loss in NCL due to a deficiency in the transmembrane protein CLN6. Read More

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http://dx.doi.org/10.1016/j.ymthe.2018.02.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993939PMC
May 2018
10 Reads

[Autistic regression: clinical and aetiological aspects].

Rev Neurol 2018 Mar;66(S01):S17-S23

Hospital de Ninos Doctor Ricardo Gutierrez, Buenos Aires, Argentina.

Introduction: Autism spectrum disorders are neurodevelopmental dysfunctions that are characterised by deficits in social integration and communication, associated with restricted interests and stereotypic behaviour. A high percentage are related to language disorders, sensory dysfunctions, attention deficit disorder, bipolarity, intellectual disability or epilepsy, among other comorbidities. It is estimated that around 30% of children with autism, with typical early development, may present regression in the first years of life, which was already reported by Kanner in one of his original cases. Read More

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March 2018
3 Reads

Loss of CLN7 results in depletion of soluble lysosomal proteins and impaired mTOR reactivation.

Hum Mol Genet 2018 05;27(10):1711-1722

Section Biochemistry, Children's Hospital, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.

Defects in the MFSD8 gene encoding the lysosomal membrane protein CLN7 lead to CLN7 disease, a neurodegenerative lysosomal storage disorder belonging to the group of neuronal ceroid lipofuscinoses. Here, we have performed a SILAC-based quantitative analysis of the lysosomal proteome using Cln7-deficient mouse embryonic fibroblasts (MEFs) from a Cln7 knockout (ko) mouse model. From 3335 different proteins identified, we detected 56 soluble lysosomal proteins and 29 highly abundant lysosomal membrane proteins. Read More

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http://dx.doi.org/10.1093/hmg/ddy076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932567PMC
May 2018
2 Reads

Evidence for Cholinergic Dysfunction in Autosomal Dominant Kufs Disease.

Can J Neurol Sci 2018 03;45(2):150-157

3Department of Medicine (Geriatric Medicine and Neurology),Dalhousie University,Halifax,Nova Scotia,Canada.

Objective: Neuronal ceroid-lipofuscinoses are a heterogeneous group of inherited disorders in which abnormal lipopigments form lysosomal inclusion bodies in neurons. Kufs disease is rare, and clinical symptoms include seizures, progressive cognitive impairment, and myoclonus. Most cases of Kufs disease are autosomal recessive; however, there have been a few case reports of an autosomal dominant form linked to mutations within the DNAJC5 gene. Read More

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http://dx.doi.org/10.1017/cjn.2017.261DOI Listing
March 2018
3 Reads
1.600 Impact Factor

Altered Expression of Ganglioside Metabolizing Enzymes Results in GM3 Ganglioside Accumulation in Cerebellar Cells of a Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis.

Int J Mol Sci 2018 Feb 22;19(2). Epub 2018 Feb 22.

Institute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, 35292 Giessen, Germany.

Juvenile neuronal ceroid lipofuscinosis (JNCL) is caused by mutations in the gene. Most JNCL patients exhibit a 1.02 kb genomic deletion removing exons 7 and 8 of this gene, which results in a truncated CLN3 protein carrying an aberrant C-terminus. Read More

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http://dx.doi.org/10.3390/ijms19020625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855847PMC
February 2018
9 Reads

Neuronal ceroid lipofuscinosis in Salukis is caused by a single base pair insertion in CLN8.

Anim Genet 2018 Feb;49(1):52-58

Section of Anatomy & Pathology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, P.O. box 8146 Dep, 0033, Oslo, Norway.

Neuronal ceroid lipofuscinoses (NCLs) are heterogenic inherited lysosomal storage diseases that have been described in a number of species including humans, sheep, cattle, cats and a number of different dog breeds, including Salukis. Here we present a novel genetic variant associated with the disease in this particular breed of dog. In a clinical case, a Saluki developed progressive neurological signs, including disorientation, anxiety, difficulties in eating, seizures and loss of vision, and for welfare reasons, was euthanized at 22 months of age. Read More

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http://dx.doi.org/10.1111/age.12629DOI Listing
February 2018
5 Reads

Identification of two novel null variants in CLN8 by targeted next-generation sequencing: first report of a Chinese patient with neuronal ceroid lipofuscinosis due to CLN8 variants.

BMC Med Genet 2018 02 8;19(1):21. Epub 2018 Feb 8.

Department of Neurology, Affiliated Children's Hospital of Capital Institute of Pediatrics, No. 2, Yabao Road, Chaoyang District, Beijing, 100020, China.

Background: Neuronal ceroid lipofuscinoses (NCLs) are one of the most frequent childhood-onset neurodegenerative pathologies characterized by seizures, progressive cognitive decline, motor impairment and loss of vision. For the past two decades, more than 430 variants in 13 candidate genes have been identified in the affected patients. Most of the variants were almost exclusively reported in Western patients, and very little clinical and genetic information was available for Chinese patients. Read More

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http://dx.doi.org/10.1186/s12881-018-0535-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806251PMC
February 2018
7 Reads

Inducible transgenic expression of tripeptidyl peptidase 1 in a mouse model of late-infantile neuronal ceroid lipofuscinosis.

PLoS One 2018 6;13(2):e0192286. Epub 2018 Feb 6.

Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey, United States of America.

Late-infantile neuronal ceroid lipofuscinosis is a fatal neurodegenerative disease of children caused by mutations resulting in loss of activity of the lysosomal protease, tripeptidyl peptidase 1 (TPP1). While Tpp1-targeted mouse models of LINCL exist, the goal of this study was to create a transgenic mouse with inducible TPP1 to benchmark treatment approaches, evaluate efficacy of treatment at different stages of disease, and to provide insights into the pathobiology of disease. A construct containing a loxP-flanked stop cassette inserted between the chicken-actin promoter and a sequence encoding murine TPP1 (TgLSL-TPP1) was integrated into the ROSA26 locus in mice by homologous recombination. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0192286PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800698PMC
April 2018
15 Reads

Timing of cognitive decline in CLN3 disease.

J Inherit Metab Dis 2018 03 1;41(2):257-261. Epub 2018 Feb 1.

Department of Metabolic Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, P.O. Box 85090, 3508, AB, Utrecht, the Netherlands.

Background: CLN3 disease is a major cause of childhood neurodegeneration. Onset of visual failure around 6 years of age is thought to precede cognitive deterioration by a few years, but casuistic reports question this paradigm. The aim of our study is to delineate timing of cognitive decline in CLN3 disease. Read More

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http://dx.doi.org/10.1007/s10545-018-0143-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830481PMC
March 2018
3 Reads

Congenital Neuronal Ceroid Lipofuscinosis with a Novel CTSD Gene Mutation: A Rare Cause of Neonatal-Onset Neurodegenerative Disorder.

Neuropediatrics 2018 Apr 28;49(2):150-153. Epub 2017 Dec 28.

Service of Genetic Medicine, University Hospitals of Geneva, Geneva, Switzerland.

Neuronal ceroid lipofuscinoses represent a heterogeneous group of early onset neurodegenerative disorders that are characterized by progressive cognitive and motor function decline, visual loss, and epilepsy. The age of onset has been historically used for the phenotypic classification of this group of disorders, but their molecular genetic delineation has now enabled a better characterization, demonstrating significant genetic heterogeneity even among individuals with a similar phenotype. The rare Congenital Neuronal Ceroid Lipofuscinosis (CLN10) caused by mutations in the gene encoding for cathepsin D is associated with a dramatic presentation with onset before or around birth. Read More

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http://www.thieme-connect.de/DOI/DOI?10.1055/s-0037-1613681
Publisher Site
http://dx.doi.org/10.1055/s-0037-1613681DOI Listing
April 2018
5 Reads

Dysregulation of autophagy as a common mechanism in lysosomal storage diseases.

Essays Biochem 2017 12 12;61(6):733-749. Epub 2017 Dec 12.

Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, U.K.

The lysosome plays a pivotal role between catabolic and anabolic processes as the nexus for signalling pathways responsive to a variety of factors, such as growth, nutrient availability, energetic status and cellular stressors. Lysosomes are also the terminal degradative organelles for autophagy through which macromolecules and damaged cellular components and organelles are degraded. Autophagy acts as a cellular homeostatic pathway that is essential for organismal physiology. Read More

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http://dx.doi.org/10.1042/EBC20170055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869865PMC
December 2017
5 Reads

The strategic function of the P5-ATPase ATP13A2 in toxic waste disposal.

Neurochem Int 2018 01 21;112:108-113. Epub 2017 Nov 21.

IQUIFIB-Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina.

The P-type ATPase ATP13A2 protein was originally associated with a form of Parkinson's Disease (PD) known as Kufor Rakeb Syndrome (KRS). However, in the last years it has been found to underlay variants of neuronal ceroid-lipofuscinoses and hereditary spastic paraplegia. These findings expand the clinical and genetic spectrum of ATP13A2-associated disorders, which are commonly characterized by lysosomal dysfunction. Read More

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http://dx.doi.org/10.1016/j.neuint.2017.11.008DOI Listing
January 2018
5 Reads

Selective depletion of microglial progranulin in mice is not sufficient to cause neuronal ceroid lipofuscinosis or neuroinflammation.

J Neuroinflammation 2017 Nov 17;14(1):225. Epub 2017 Nov 17.

Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Children's and Women's Hospital, 980 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada.

Background: Progranulin deficiency due to heterozygous null mutations in the GRN gene are a common cause of familial frontotemporal lobar degeneration (FTLD), while homozygous loss-of-function GRN mutations are thought to be a rare cause of neuronal ceroid lipofuscinosis (NCL). Aged progranulin-knockout (Grn-null) mice display highly exaggerated lipofuscinosis, microgliosis, and astrogliosis, as well as mild cell loss in specific brain regions. In the brain, progranulin is predominantly expressed in neurons and microglia, and previously, we demonstrated that neuronal-specific depletion of progranulin does not recapitulate the neuropathological phenotype of Grn-null mice. Read More

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http://dx.doi.org/10.1186/s12974-017-1000-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693502PMC
November 2017
8 Reads

Defective synaptic transmission causes disease signs in a mouse model of juvenile neuronal ceroid lipofuscinosis.

Elife 2017 11 14;6. Epub 2017 Nov 14.

Hans-Berger Department of Neurology, Jena University Hospital, Jena, Germany.

Juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease) caused by mutations in the gene is the most prevalent inherited neurodegenerative disease in childhood resulting in widespread central nervous system dysfunction and premature death. The consequences of mutation on the progression of the disease, on neuronal transmission, and on central nervous network dysfunction are poorly understood. We used knockout ( mice and found increased anxiety-related behavior and impaired aversive learning as well as markedly affected motor function including disordered coordination. Read More

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http://dx.doi.org/10.7554/eLife.28685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5724993PMC
November 2017
21 Reads

Cln5 is secreted and functions as a glycoside hydrolase in Dictyostelium.

Cell Signal 2018 Jan 8;42:236-248. Epub 2017 Nov 8.

Trent University, Department of Biology, 1600 West Bank Drive, Peterborough, Ontario K9L 0G2, Canada. Electronic address:

Ceroid lipofuscinosis neuronal 5 (CLN5) is a member of a family of proteins that are linked to neuronal ceroid lipofuscinosis (NCL). This devastating neurological disorder, known commonly as Batten disease, affects all ages and ethnicities and is currently incurable. The precise function of CLN5, like many of the NCL proteins, remains to be elucidated. Read More

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http://dx.doi.org/10.1016/j.cellsig.2017.11.001DOI Listing
January 2018
14 Reads

Novel compound heterozygous mutations causing Kufs disease type B.

Int J Neurosci 2018 Jun 22;128(6):573-576. Epub 2017 Nov 22.

a Department of Clinical Laboratory , The First Affiliated Hospital of Zhengzhou University , Zhengzhou , China.

Background: Kufs disease type B (also termed CLN13), an adult-onset form of neuronal ceroid lipofuscinosis (NCL), is genetically heterogeneous and challenging to diagnose. Recently, mutations in cathepsin-F have been identified as the causative gene for autosomal recessive Kufs disease type B.

Results: Here, we report a sporadic case of Kufs disease type B with novel compound heterozygous mutations, a novel missense mutation c. Read More

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http://dx.doi.org/10.1080/00207454.2017.1403439DOI Listing
June 2018
8 Reads

Lack of specificity of antibodies raised against CLN3, the lysosomal/endosomal transmembrane protein mutated in juvenile Batten disease.

Biosci Rep 2017 Dec 23;37(6). Epub 2017 Nov 23.

Pediatric and Rare Diseases Group, Sanford Research, Sioux Falls, South Dakota 57104, U.S.A.

Juvenile CLN3 (Batten) disease, a fatal, childhood neurodegenerative disorder, results from mutations in the gene encoding a lysosomal/endosomal transmembrane protein. The exact physiological function of CLN3 is still unknown and it is unclear how mutations lead to selective neurodegeneration. To study the tissue expression and subcellular localization of the CLN3 protein, a number of anti-CLN3 antibodies have been generated using either the whole CLN3 protein or short peptides from CLN3 for immunization. Read More

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http://bioscirep.org/lookup/doi/10.1042/BSR20171229
Publisher Site
http://dx.doi.org/10.1042/BSR20171229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700270PMC
December 2017
11 Reads