84,357 results match your criteria neurodegeneration neurobehavioral

Positive effects of roflumilast on behavior, neuroinflammation, and white matter injury in mice with global cerebral ischemia.

Behav Pharmacol 2021 Jul 26. Epub 2021 Jul 26.

Department of Pharmacology and Therapeutics, State University of Maringá, Paraná, Brazil Neuroimmune Connect and Repair Lab., Biomedical Research Institute, Hasselt University, Hasselt, Belgium Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.

Inhibition of phosphodiesterase 4 (PDE4) is a promising pharmacological strategy for the treatment of cerebral ischemic conditions. To increase the relevance and increase the translational value of preclinical studies, it is important to conduct experiments using different animal species and strains, different animal models, and to evaluate long-term functional outcomes after cerebral ischemia. In the present study, the effects of the selective PDE4 inhibitor roflumilast were evaluated in vivo and in vitro. Read More

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Associations of increased interstitial fluid with vascular and neurodegenerative abnormalities in a memory clinic sample.

Neurobiol Aging 2021 Jul 5;106:257-267. Epub 2021 Jul 5.

Department of Radiology & Nuclear Medicine, Maastricht University Medical Center, Maastricht, the Netherlands; School for Mental Health & Neuroscience, Alzheimer Center Limburg, Maastricht, the Netherlands; Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands. Electronic address:

The vascular and neurodegenerative processes related to clinical dementia cause cell loss which induces, amongst others, an increase in interstitial fluid (ISF). We assessed microvascular, parenchymal integrity, and a proxy of ISF volume alterations with intravoxel incoherent motion imaging in 21 healthy controls and 53 memory clinic patients - mainly affected by neurodegeneration (mild cognitive impairment, Alzheimer's disease dementia), vascular pathology (vascular cognitive impairment), and presumed to be without significant pathology (subjective cognitive decline). The microstructural components were quantified with spectral analysis using a non-negative least squares method. Read More

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NIR Laser Photobiomodulation Induces Neuroprotection in an In Vitro Model of Cerebral Hypoxia/Ischemia.

Mol Neurobiol 2021 Jul 28. Epub 2021 Jul 28.

Department of Neuroscience, Psychology, Drug Research and Child Health (NeuroFarBa), Section of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini 6, 50139, Florence, Italy.

Brain photobiomodulation (PBM) is an innovative treatment for a variety of neurological conditions, including cerebral ischemia. However, the capability of PBM for ischemic stroke needs to be further explored and its mechanisms of action remain currently unclear. The aim of the present research was to identify a treatment protocol capable of inducing neuroprotection and to investigate the molecular mechanisms activated by a dual-wavelength near infrared (NIR) laser source in an organotypic hippocampal slice model of hypoxia/ischemia. Read More

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Flavan-3-ol Microbial Metabolites Modulate Proteolysis in Neuronal Cells Reducing Amyloid-beta (1-42) Levels.

Mol Nutr Food Res 2021 Jul 28:e2100380. Epub 2021 Jul 28.

School of Biosciences and Veterinary Medicine, University of Camerino, Italy.

Scope: Alzheimer's disease (AD) is a progressive neurodegeneration characterized by extensive protein aggregation and deposition in the brain, associated with defective proteasomal and autophagic-lysosomal proteolytic pathways. Since current drugs can only reduce specific symptoms, the identification of novel treatments is a major concern in AD research. Among natural compounds, (poly)phenols and their derivatives/metabolites are emerging as candidates in AD prevention due to their multiple beneficial effects. Read More

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Protonation-Deprotonation Switch Controls the Amyloid-like Misfolding of Nucleic-Acid-Binding Domains of TDP-43.

J Phys Chem B 2021 Jul 28. Epub 2021 Jul 28.

Physical and Materials Chemistry Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India.

Nutrient starvation stress acidifies the cytosol and leads to the formation of large protein assemblies and misfolded aggregates. However, how starvation stress is sensed at the molecular level and leads to protein misfolding is poorly understood. TDP-43 is a vital protein, which, under stress-like conditions, associates with stress granule proteins via its functional nucleic-acid-binding domains (TDP-43) and misfolds to form aberrant aggregates. Read More

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Humoral response to neurofilaments and dipeptide repeats in ALS progression.

Ann Clin Transl Neurol 2021 Jul 27. Epub 2021 Jul 27.

Neurodegeneration Group, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT, United Kingdom.

Objective: To appraise the utility as biomarkers of blood antibodies and immune complexes to neurofilaments and dipeptide repeat proteins, the products of translation of the most common genetic mutation in amyotrophic lateral sclerosis (ALS).

Methods: Antibodies and immune complexes against neurofilament light, medium, heavy chains as well as poly-(GP)-(GR) dipeptide repeats were measured in blood samples from the ALS Biomarkers (n = 107) and the phenotype-genotype biomarker (n = 129) studies and in 140 healthy controls. Target analyte levels were studied longitudinally in 37 ALS cases. Read More

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The emerging roles of long non-coding RNAs in polyglutamine diseases.

J Cell Mol Med 2021 Jul 28. Epub 2021 Jul 28.

Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, China.

Polyglutamine (polyQ) diseases are characterized by trinucleotide repeat amplifications within genes, thus resulting in the formation of polyQ peptides, selective neuronal degeneration and possibly death due to neurodegenerative diseases (NDDs). Long non-coding RNAs (lncRNAs), which exceed 200 nucleotides in length, have been shown to play important roles in several pathological processes of NDDs, including polyQ diseases. Some lncRNAs have been consistently identified to be specific to polyQ diseases, and circulating lncRNAs are among the most promising novel candidates in the search for non-invasive biomarkers for the diagnosis and prognosis of polyQ diseases. Read More

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Neurodegenerative movement disorders: an epigenetics perspective and promise for the future.

Neuropathol Appl Neurobiol 2021 Jul 27. Epub 2021 Jul 27.

Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London, UK.

Neurodegenerative movement disorders (NMDs) are age dependent disorders that are characterised by the degeneration and loss of neurons, typically accompanied by pathological accumulation of different protein aggregates in the brain, which lead to motor symptoms. NMDs include Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, and Huntington's disease, among others. Epigenetic modifications are responsible for functional gene regulation during development, adult life, and ageing, and have progressively been implicated in complex diseases such as cancer, and more recently in neurodegenerative diseases, such as NMDs. Read More

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Activation of the Protein Kinase R-Like Endoplasmic Reticulum Kinase (PERK) Pathway of the Unfolded Protein Response after Experimental Traumatic Brain Injury and Treatment with a PERK Inhibitor.

Neurotrauma Rep 2021 6;2(1):330-342. Epub 2021 Jul 6.

Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.

Neurodegeneration after traumatic brain injury (TBI) is increasingly recognized as a key factor contributing to poor chronic outcomes. Activation (i.e. Read More

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Huntington disease: Advances in the understanding of its mechanisms.

Clin Park Relat Disord 2020 6;3:100056. Epub 2020 May 6.

National Administration of Laboratories and Institutes of Health, ANLIS, Dr. Carlos G. Malbrán, Argentina.

Huntington disease (HD) is a devastating monogenic autosomal dominant disorder. HD is caused by a CAG expansion in exon 1 of the gene coding for huntingtin, placed in the short arm of chromosome 4. Despite its well-defined genetic origin, the molecular and cellular mechanisms underlying the disease are unclear and complex. Read More

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Nutritional ketosis for mild cognitive impairment in Parkinson's disease: A controlled pilot trial.

Clin Park Relat Disord 2019 6;1:41-47. Epub 2019 Aug 6.

James J and Joan A Gardner Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati Academic Health Center, Cincinnati, OH, USA.

Introduction: Glucose hypometabolism and insulin resistance increase risk for and accelerate progression in Parkinson's disease and neurocognitive disorders. We conducted a proof of concept trial to determine whether ketogenesis, a metabolic adaptation induced by dietary carbohydrate restriction, can improve cognitive performance in Parkinson's disease patients with mild cognitive impairment.

Methods: We enrolled patients with mild cognitive impairment associated with Parkinson's disease in an eight-week nutritional intervention with random assignment to either high-carbohydrate consumption typical of the Western dietary pattern ( = 7) or to a low-carbohydrate, ketogenic regimen ( = 7). Read More

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Validating the Vietnamese version of wearing - Off 19 questionnaire for patients with Parkinson's disease.

Clin Park Relat Disord 2019 5;1:37-40. Epub 2019 Aug 5.

The Truong Neuroscience Institute, Orange Coast Memorial Medical Center, Fountain Valley, CA 92708, USA.

Background: One of the most common complication of the progression of Parkinson's disease (PD) is the wearing off phenomenon. A validated Vietnamese version of Wearing off 19 (WO19) questionnaire is necessary to optimize the Vietnamese PD treatment.

Objectives: This study was undertaken to determine the quality attribute of the questionnaire as a tool for early detection of wearing off (WO) in Vietnamese population with PD. Read More

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Cervical dystonia: Injecting botulinum neurotoxin into semispinalis capitis improves goose-neck posture.

Clin Park Relat Disord 2019 15;1:8-9. Epub 2019 Jul 15.

The Parkinson and Movement Disorder Institute, Fountain Valley, CA 92708, USA.

We describe a patient with goose-neck posture as the presenting form of cervical dystonia. In our case, the bilateral semispinalis capitis muscles were hypertrophic, thick, and overactive while both splenius capitis and sternocleidomastoid muscles were normal. In this single case experience, we demonstrated that the semispinalis capitis muscle may play a primary role in causing a goose-neck posture and the observed forward sagittal shift may be a compensatory or overflow activity of neck flexor muscles. Read More

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Tripchlorolide attenuates β-amyloid generation by inducing NEP activity in N2a/APP695 cells.

Transl Neurosci 2021 Jan 20;12(1):301-308. Epub 2021 Jul 20.

Department of Neurology, Institute of Clinical Neurology, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian, 350001, China.

Background And Purpose: Alzheimer's disease (AD) is a neurodegeneration disease. The previous work from our research group demonstrated the neuroprotective effects of tripchlorolide (T4) in AD animal models.

Materials And Methods: Neprilysin (NEP) is known as an important physiological amyloid-β protein (Aβ) peptide-degrading enzyme in the brain due to its apparent rate-limiting function. Read More

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January 2021

Spastic Paraplegia-56 due to a Novel CYP2U1 Truncating Mutation in an Indian Boy: A New Report and Literature Review.

J Pediatr Neurosci 2021 Jan-Mar;16(1):71-74. Epub 2021 Jun 25.

Department of Pediatrics, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Spastic paraplegia-56 is a rare autosomal recessive disorder, caused by homozygous or compound heterozygous mutations in the gene, located on chromosome 4. Till date, only 28 patients with this disorder have been reported in the literature. We report a new case of CYP2U1-related spastic paraplegia-56. Read More

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Clinical and histopathological studies on neurodegeneration and dysautonomia in buffalo calves during foot-and-mouth disease outbreaks in Egypt.

Vet World 2021 Jun 23;14(6):1622-1630. Epub 2021 Jun 23.

Department of Animal Medicine, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.

Background And Aim: Signs of dysautonomia were frequently observed in calves that died during foot-and-mouth disease (FMD) virus (FMDV) outbreaks in Egypt from 2015 to 2018. This study aimed to describe the clinical and histopathological features of the central nervous system in malignant cases of FMD and excluding possible concurrent bacterial, and bovine herpes virus 4 (BHV4) infections or both.

Materials And Methods: In this study, 335 FMDV-infected buffalo calves aged 1-22 months were clinically examined and followed until recovery or death. Read More

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Shotgun lipidomics of liver and brain tissue of Alzheimer's disease model mice treated with acitretin.

Sci Rep 2021 Jul 27;11(1):15301. Epub 2021 Jul 27.

Experimental Neurology, Saarland University, Homburg, Saar, Germany.

Alzheimer's disease (AD) is a very frequent neurodegenerative disorder characterized by an accumulation of amyloid-β (Aβ). Acitretin, a retinoid-derivative and approved treatment for Psoriasis vulgaris, increases non-amyloidogenic Amyloid-Precursor-Protein-(APP)-processing, prevents Aβ-production and elicits cognitive improvement in AD mouse models. As an unintended side effect, acitretin could result in hyperlipidemia. Read More

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Dysregulation of the AP2M1 phosphorylation cycle by LRRK2 impairs endocytosis and leads to dopaminergic neurodegeneration.

Sci Signal 2021 Jul 27;14(693). Epub 2021 Jul 27.

Department of Neuroscience, University of Connecticut School of Medicine, Farmington, CT 06030, USA.

Mutations in the kinase LRRK2 and impaired endocytic trafficking are both implicated in the pathogenesis of Parkinson's disease (PD). Expression of the PD-associated LRRK2 mutant in mouse dopaminergic neurons was shown to disrupt clathrin-mediated endocytic trafficking. Here, we explored the molecular mechanism linking LRRK2 to endocytosis and found that LRRK2 bound to and phosphorylated the μ2 subunit of the adaptor protein AP2 (AP2M1), a core component of the clathrin-mediated endocytic machinery. Read More

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Evaluation and categorisation of individual patients based on white matter profiles: Single-patient diffusion data interpretation in neurodegeneration.

J Neurol Sci 2021 Jul 21;428:117584. Epub 2021 Jul 21.

Computational Neuroimaging Group, Trinity College Dublin, Dublin, Ireland; Pitié-Salpêtrière University Hospital, Sorbonne University, Paris, France. Electronic address:

The majority of radiology studies in neurodegenerative conditions infer group-level imaging traits from group comparisons. While this strategy is helpful to define phenotype-specific imaging signatures for academic use, the meaningful interpretation of single scans of individual subjects is more important in everyday clinical practice. Accordingly, we present a computational method to evaluate individual subject diffusion tensor data to highlight white matter integrity alterations. Read More

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A vicious cycle of neuropathological, cognitive and behavioural sequelae of repeated opioid overdose.

Int J Drug Policy 2021 Jul 24;97:103362. Epub 2021 Jul 24.

Dornsife School of Public Health, Drexel University, Philadelphia, PA 19104, USA.

In the midst of an escalating U.S. opioid crisis, the immediate focus of public health interventions is on fatal overdose prevention. Read More

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Revealing NOTCH-dependencies in synaptic targets associated with Alzheimer's disease.

Mol Cell Neurosci 2021 Jul 24:103657. Epub 2021 Jul 24.

Section of Medicine, Department NMS, University of Fribourg, Fribourg, Switzerland; Swiss Integrative Center for Human Health, Fribourg, Switzerland. Electronic address:

Recent studies have identified NOTCH signaling as a contributor of neurodegeneration including Alzheimer's disease' (AD) pathophysiology. As part of the efforts to understand molecular mechanisms and players involved in neurodegenerative dementia, we employed transgenic mouse models with Notch1 and Rbpjk loss of function (LOF) mutation in pyramidal neurons of the CA fields. Using RNA-seq, we have investigated the differential expression of NOTCH-dependent genes either upon environmental enrichment (EE) or upon kainic acid (KA) injury. Read More

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Content-specific vulnerability of recent episodic memories in Alzheimer's disease.

Neuropsychologia 2021 Jul 24:107976. Epub 2021 Jul 24.

Institute of Cognitive Neurology and Dementia Research, Otto von Guericke University Magdeburg, Germany; German Center for Neurodegenerative Diseases Magdeburg, Germany; Institute of Cognitive Neuroscience, University College London, United Kingdom. Electronic address:

Endel Tulving's episodic memory framework emphasizes the multifaceted re-experiencing of personal events. Indeed, decades of research focused on the experiential nature of episodic memories, usually treating recent episodic memory as a coherent experiential quality. However, recent insights into the functional architecture of the medial temporal lobe show that different types of mnemonic information are segregated into distinct neural pathways in brain circuits empirically associated with episodic memory. Read More

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Availability of neuregulin-1beta1 protects neurons in spinal cord injury and against glutamate toxicity through caspase dependent and independent mechanisms.

Exp Neurol 2021 Jul 24:113817. Epub 2021 Jul 24.

Department of Physiology and Pathophysiology, Regenerative Medicine Program, Spinal Cord Research Centre, Children's Hospital Research Institute of Manitoba, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. Electronic address:

Spinal cord injury (SCI) causes sensorimotor and autonomic impairment that partly reflects extensive, permanent loss of neurons at the epicenter and penumbra of the injury. Strategies aimed at enhancing neuronal protection are critical to attenuate neurodegeneration and improve neurological recovery after SCI. In rat SCI, we previously uncovered that the tissue levels of neuregulin-1beta 1 (Nrg-1β1) are acutely and persistently downregulated in the injured spinal cord. Read More

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ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids.

Cell 2021 Jul 21. Epub 2021 Jul 21.

Neural Stem Cell Institute, Rensselaer, NY 12144, USA. Electronic address:

Frontotemporal dementia (FTD) because of MAPT mutation causes pathological accumulation of tau and glutamatergic cortical neuronal death by unknown mechanisms. We used human induced pluripotent stem cell (iPSC)-derived cerebral organoids expressing tau-V337M and isogenic corrected controls to discover early alterations because of the mutation that precede neurodegeneration. At 2 months, mutant organoids show upregulated expression of MAPT, glutamatergic signaling pathways, and regulators, including the RNA-binding protein ELAVL4, and increased stress granules. Read More

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Insomnia symptom subtypes and manifestations of prodromal neurodegeneration: a population-based study in the CLSA.

J Clin Sleep Med 2021 Jul 27. Epub 2021 Jul 27.

Research center of the Hôpital du Sacré-Coeur de Montréal, Montreal, QC, Canada.

Study Objectives: To identify the association between insomnia symptoms and signs of prodromal neurodegeneration, including an analysis of potential differences between sleep-onset and sleep-maintenance insomnia.

Methods: We included those aged 45-85 years, living in one of 10 Canadian provinces in between 2012-2015 (at the baseline), recruited via three population-based sampling methods. Insomnia symptoms were assessed using questions adapted/modified from the Pittsburgh Sleep Quality Index. Read More

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Inhibition of the HIF-1α/BNIP3 pathway has a retinal neuroprotective effect.

FASEB J 2021 08;35(8):e21829

Laboratory of Photobiology, Keio University School of Medicine, Shinanomachi, Japan.

Retinal ischemia is a leading cause of irreversible blindness worldwide. Inner retinal dysfunction including loss of retinal ganglion cells is encountered in a number of retinal ischemic disorders. We previously reported administration of two different hypoxia-inducible factor (HIF) inhibitors exerted neuroprotective effects in a murine model of retinal ischemia/reperfusion (I/R) which mimics these disorders, as inner retinal degeneration could be involved in pathological HIF induction. Read More

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Role of metals in Alzheimer's disease.

Metab Brain Dis 2021 Jul 27. Epub 2021 Jul 27.

Division of Neurotoxicology HFT-132, National Center for Toxicological Research/Food and Drug Administration, Jefferson, AR, 72079, USA.

Metal homeostasis in the central nervous system (CNS) is a crucial component of healthy brain function, because metals serve as enzymatic cofactors and are key components of intra- and inter-neuronal signaling. Metal dysregulation wreaks havoc on neural networks via induction and proliferation of pathological pathways that cause oxidative stress, synaptic impairment, and ultimately, cognitive deficits. Thus, exploration of metal biology in relation to neurodegenerative pathology is essential in pursuing novel therapies for Alzheimer's Disease and other neurodegenerative disorders. Read More

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Neurite Imaging Reveals Widespread Alterations in Gray and White Matter Neurite Morphology in Healthy Aging and Amnestic Mild Cognitive Impairment.

Cereb Cortex 2021 Jul 27. Epub 2021 Jul 27.

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94304, USA.

Aging is the major risk factor for neurodegenerative diseases and affects neurite distributions throughout the brain, yet underlying neurobiological mechanisms remain unclear. Multi-shell diffusion-weighted imaging and neurite orientation dispersion and density imaging (NODDI) now provide in vivo biophysical measurements that explain these biological processes in the cortex and white matter. In this study, neurite distributions were evaluated in the cortex and white matter in healthy older adults and patients with amnestic mild cognitive impairment (aMCI) that provides fundamental contributions regarding healthy aging and neurodegeneration. Read More

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Automated Retinal Layer Segmentation in CLN2-Associated Disease: Commercially Available Software Characterizing a Progressive Maculopathy.

Transl Vis Sci Technol 2021 Jul;10(8):23

Department of Ophthalmology, Retina Service, Weill Cornell Medical College, New York, NY, USA.

Purpose: CLN2-associated disease is a hereditary, fatal lysosomal storage disorder characterized by progressive brain and retinal deterioration. Here, we characterize the inner and outer retinal degeneration using automated segmentation software in optical coherence tomography scans, providing an objective, quantifiable metric for monitoring subtle changes previously identified with a validated disease classification scale (the Weill Cornell Batten Scale).

Methods: This study is a retrospective, single-center cohort review of images from examinations under anesthesia in treatment-naïve patients with CLN2-associated disease. Read More

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ATG7 safeguards human neural integrity.

Autophagy 2021 Jul 27:1-3. Epub 2021 Jul 27.

Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.

ATG7 drives macroautophagy, hereafter "autophagy", by generating ATG12-ATG5 conjugates and lipidating Atg8 homologs including LC3. A pioneering body of work has defined the requirement of ATG7 for survival in mice and shown that neural-specific deletion causes neurodegeneration, but it has not been ascertained whether human life is compatible with ATG7 dysfunction. Recently, we defined the importance of ATG7 in human physiology by identifying twelve patients from five families harboring pathogenic, biallelic variants causing a neurodevelopmental disorder. Read More

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