ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2002
Deregulation of cdk5, hyperphosphorylation, and cytoskeletal pathology in the Niemann-Pick type C murine model.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
What it found
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Who cites it
82 citing papers in PubMed, 191 citations in OpenAlex.
- Multi-omics reveal phosphatidic acid phosphatases modify Niemann-Pick type C disease severity.iScience · 2026Article
- The Recycling Endosomal (NaActa physiologica (Oxford, England) · 2026Article
- Targeting a Tau Kinase Cdk5, Cyclin-Dependent Kinase: A Blood-Based Diagnostic Marker and Therapeutic Earmark for Alzheimer's Disease.Biomolecules · 2025Article
- MAP2 phosphorylation: mechanisms, functional consequences, and emerging insights.Frontiers in cellular neuroscience · 2025Review
- Unraveling the Connection: Cholesterol, Calcium Signaling, and Neurodegeneration.Neuroscience insights · 2024Article
- Mitigating aberrant Cdk5 activation alleviates mitochondrial defects and motor neuron disease symptoms in spinal muscular atrophy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- NPC1-dependent alterations in KNature communications · 2023Article
- MicroRNA-650 Regulates the Pathogenesis of Alzheimer's Disease Through Targeting Cyclin-Dependent Kinase 5.Molecular neurobiology · 2023Article
- Severe neurometabolic phenotype inFrontiers in molecular neuroscience · 2023Article
- Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms.Frontiers in aging neuroscience · 2022Review
- Maternal sevoflurane exposure induces neurotoxicity in offspring ratsFrontiers in pharmacology · 2022Article
- Differential involvement of hippocampal subfields in Niemann-Pick type C disease: a case-control study.Metabolic brain disease · 2021Article
- Haploinsufficiency of tau decreases survival of the mouse model of Niemann-Pick disease type C1 but does not alter tau phosphorylation.Journal of applied genetics · 2020Article
- Effects of Different Continuous Aerobic Training Protocols in a Heterozygous Mouse Model of Niemann-Pick Type C Disease.Journal of functional morphology and kinesiology · 2020Article
- Targeting Tau to Treat Clinical Features of Huntington's Disease.Frontiers in neurology · 2020Review
- Loss in efficacy measures of tolfenamic acid in a tau knock-out model: Relevance to Alzheimer's disease.Experimental biology and medicine (Maywood, N.J.) · 2019Article
- Maternal Choline Supplementation Alters Basal Forebrain Cholinergic Neuron Gene Expression in the Ts65Dn Mouse Model of Down Syndrome.Developmental neurobiology · 2019Article
- Imaging of tau deposits in adults with Niemann-Pick type C disease: a case-control study.European journal of nuclear medicine and molecular imaging · 2019Article
- Development of AD-Like Pathology in Skeletal Muscle.Journal of Parkinson's disease and Alzheimer's disease · 2019Article
- Aberrant activation of Cdc2/cyclin B1 is involved in initiation of cytoskeletal pathology in murine Niemann-Pick disease type C.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2017Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
NPC-1 gene mutations cause Niemann-Pick type C (NPC), a neurodegenerative storage disease resulting in premature death in humans. Spontaneous mutation of the NPC-1 gene in mice generates a similar phenotype, usually with death ensuing by 12 weeks of age. Both human and murine NPC are characterized neuropathologically by ballooned neurons distended with lipid storage, axonal spheroid formation, demyelination, and widespread neuronal loss. To elucidate the biochemical mechanism underlying this neuropathology, we have investigated the phosphorylation of neuronal cytoskeletal proteins in the brains of npc-1 mice. A spectrum of antibodies against phosphorylated epitopes in neurofilaments (NFs) and MAP2 and tau were used in immunohistochemical and immunoblotting analyses of 4- to 12-week-old mice. Multiple sites in NFs, MAP2, and tau were hyperphosphorylated as early as 4 weeks of age and correlated with a significant increase in activity of the cyclin-dependent kinase 5 (cdk5) and accumulation of its more potent activator, p25, a proteolytic fragment of p35. At 5 weeks of age, the development of axonal spheroids was noted in the pons. p25 and cdk5 coaccumulated with hyperphosphorylated cytoskeletal proteins in axon spheroids. These various abnormalities escalated with each additional week of age, spreading to other regions of the brainstem, basal ganglia, cerebellum, and eventually, the cortex. Our data suggest that focal deregulation of cdk5/p25 in axons leads to cytoskeletal abnormalities and eventual neurodegeneration in NPC. The npc-1 mouse is a valuable in vivo model for determining how and when cdk5 becomes deregulated and whether cdk5 inhibitors would be useful in blocking NPC neurodegeneration.
Indexed as
Identifiers
12151531PMC6758154W2151498829What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.