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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

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

Lancet Neurol 2018 Nov 20. Epub 2018 Nov 20.

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

Biochim Biophys Acta Mol Basis Dis 2018 Nov 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

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

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

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

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

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

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

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

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

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

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

Expert Opin Biol Ther 2018 Jul 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

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

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

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

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

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

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

Mol Ther 2018 May 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Acta Neuropathol Commun 2017 10 17;5(1):74. Epub 2017 Oct 17.

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 or Batten disease) are a group of inherited, fatal neurodegenerative disorders of childhood. In these disorders, glial (microglial and astrocyte) activation typically occurs early in disease progression and predicts where neuron loss subsequently occurs. We have found that in the most common juvenile form of NCL (CLN3 disease or JNCL) this glial response is less pronounced in both mouse models and human autopsy material, with the morphological transformation of both astrocytes and microglia severely attenuated or delayed. Read More

Hum Mol Genet 2017 12;26(24):4861-4872

The Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.

Frontotemporal dementia (FTD) encompasses a group of neurodegenerative disorders characterized by cognitive and behavioral impairments. Heterozygous mutations in progranulin (PGRN) cause familial FTD and result in decreased PGRN expression, while homozygous mutations result in complete loss of PGRN expression and lead to the neurodegenerative lysosomal storage disorder neuronal ceroid lipofuscinosis (NCL). However, how dose-dependent PGRN mutations contribute to these two different diseases is not well understood. Read More

Arq Bras Oftalmol 2017 Jul-Aug;80(4):215-219

Laboratório de Eletrofisiologia Visual Clínica, Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.

Purpose:: To analyze the clinical features, visual acuity, and full-field electroretinogram (ERG) findings of 15 patients with the neuronal ceroid lipofuscinosis (NCL) phenotype and to establish the role of ERG testing in NCL diagnosis.

Methods:: The medical records of five patients with infantile NCL, five with Jansky-Bielschowsky disease, and five with juvenile NCL who underwent full-field ERG testing were retrospectively analyzed.

Results:: Progressive vision loss was the initial symptom in 66. Read More

Cell Rep 2017 Sep;20(11):2565-2574

Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address:

Defective lysosomal function defines many neurodegenerative diseases, such as neuronal ceroid lipofuscinoses (NCL) and Niemann-Pick type C (NPC), and is implicated in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD-TDP) with progranulin (PGRN) deficiency. Here, we show that PGRN is involved in lysosomal homeostasis and lipid metabolism. PGRN deficiency alters lysosome abundance and morphology in mouse neurons. Read More

Neurobiol Dis 2017 Dec 30;108:277-287. Epub 2017 Aug 30.

Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA.

The neuronal ceroid lipofuscinoses (NCLs) are devastating inherited progressive neurodegenerative diseases, with most forms having a childhood onset of clinical signs. The NCLs are characterized by progressive cognitive and motor decline, vision loss, seizures, respiratory and swallowing impairment, and ultimately premature death. Different forms of NCL result from mutations in at least 13 genes. Read More

J Mol Neurosci 2017 Sep 15;63(1):100-114. Epub 2017 Aug 15.

Seneb Bioscience, Inc., Pennsylvania Biotechnology Center, 3805 Old Easton Road, Doylestown, PA, 18902, USA.

Juvenile Batten disease (JBD) is an inherited disorder that is characterized by the development of blindness, seizures, and progressive motor, psychiatric, and cognitive impairment. A model of JBD expressing the predominant human mutation (Cln3 ) has been explored. Dissociated brain cultures from Cln3 knock-in mice were compared to wild type (WT) for effects on granules of ceroid lipofuscin (CL) and neuronal structure. Read More

J Proteome Res 2017 10 28;16(10):3787-3804. Epub 2017 Aug 28.

Center for Advanced Biotechnology and Medicine , Piscataway, New Jersey 08854, United States.

Clinical trials have been conducted for the neuronal ceroid lipofuscinoses (NCLs), a group of neurodegenerative lysosomal diseases that primarily affect children. Whereas clinical rating systems will evaluate long-term efficacy, biomarkers to measure short-term response to treatment would be extremely valuable. To identify candidate biomarkers, we analyzed autopsy brain and matching CSF samples from controls and three genetically distinct NCLs due to deficiencies in palmitoyl protein thioesterase 1 (CLN1 disease), tripeptidyl peptidase 1 (CLN2 disease), and CLN3 protein (CLN3 disease). Read More

Dis Model Mech 2017 09 21;10(9):1089-1100. Epub 2017 Jul 21.

A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland

Neural stem/progenitor cells (NPCs) generate new neurons in the brain throughout an individual's lifetime in an intricate process called neurogenesis. Neurogenic alterations are a common feature of several adult-onset neurodegenerative diseases. The neuronal ceroid lipofuscinoses (NCLs) are the most common group of inherited neurodegenerative diseases that mainly affect children. Read More

Proc Natl Acad Sci U S A 2017 07 3;114(29):E5920-E5929. Epub 2017 Jul 3.

Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 9RX, United Kingdom;

Infantile neuronal ceroid lipofuscinosis (INCL, or CLN1 disease) is an inherited neurodegenerative storage disorder caused by a deficiency of the lysosomal enzyme palmitoyl protein thioesterase 1 (PPT1). It was widely believed that the pathology associated with INCL was limited to the brain, but we have now found unexpectedly profound pathology in the human INCL spinal cord. Similar pathological changes also occur at every level of the spinal cord of PPT1-deficient ( ) mice before the onset of neuropathology in the brain. Read More

Neurobiol Dis 2017 Oct 21;106:14-22. Epub 2017 Jun 21.

Centre for Molecular Medicine & 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; Division of Neurology, Department of Medicine, University of British Columbia Hospital, S 192 - 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada; Brain Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Electronic address:

Progranulin deficiency due to heterozygous null mutations in the GRN gene is a common cause of familial frontotemporal lobar degeneration (FTLD), while homozygous loss-of-function GRN mutations cause neuronal ceroid lipofuscinosis (NCL). Aged progranulin-knockout mice display highly exaggerated lipofuscinosis, microgliosis, and astrogliosis, as well as mild cell loss in specific brain regions. Progranulin is a secreted glycoprotein expressed in both neurons and microglia, but not astrocytes, in the brain. Read More

Epilepsia 2017 08 20;58(8):1380-1388. Epub 2017 Jun 20.

Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS (Istituto di Ricerca e Cura a Carattere Scientifico), Rome, Italy.

Objective: This study aimed to identify early clinical, magnetic resonance imaging (MRI), and electroencephalographic (EEG) characteristics of neuronal ceroid lipofuscinosis type 2 (CLN2) disease to enable early diagnosis, thus providing the key to early treatment, and optimized care and outcomes.

Methods: Retrospective clinical chart review of a series of patients diagnosed with CLN2 disease from 2005 to 2015 at a single center in Italy. Clinical, MRI, and EEG findings were reviewed. Read More

Mol Ther 2017 08 16;25(8):1743-1745. Epub 2017 Jun 16.

Department of Pediatrics, Los Angeles Biomedical Research Institute, David Geffen School of Medicine, UCLA, 1124 W Carson St., Torrance, CA 90502, USA.

Orphanet J Rare Dis 2017 06 17;12(1):113. Epub 2017 Jun 17.

Rush University Medical Center, Chicago, IL, USA.

Neuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease, is a group of genetically distinct lysosomal disorders that mainly affect the central nervous system, resulting in progressive motor and cognitive decline primarily in children. Multiple distinct genes involved in the metabolism of lipids have been identified to date with various mutations in this family of diseases. There is no cure for these diseases but some new therapeutic approaches have been tested that offer more hope than the standard palliative care. Read More