ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2003
Alzheimer's presenilin 1 mutations impair kinesin-based axonal transport.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers.
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Who cites it
149 citing papers in PubMed, 301 citations in OpenAlex.
- The Interplay of Metabolic Dysfunction, Neuroinflammation, and Mitochondrial Dysfunction in Balance Impairment: Insights from Type 2 Diabetes Mellitus and Alzheimer's Disease.Molecular neurobiology · 2026Review
- Bisphenol-A impairs hippocampal neurogenesis by disrupting kinesin-1-dependent mitochondrial trafficking.The Journal of biological chemistry · 2026Article
- SKOOTS: Skeleton-Oriented Object Segmentation for Mitochondria in High-Resolution Cochlear EM Datasets.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Pathological Calcium Signaling in Traumatic Brain Injury and Alzheimer's Disease: From Acute Neuronal Injury to Chronic Neurodegeneration.International journal of molecular sciences · 2025Review
- Harnessing Metabolism to Combat Neurodegeneration: Strategies for Reversing Age-Related Cognitive Decline.ACS pharmacology & translational science · 2025Review
- SKOOTS: Skeleton-oriented object segmentation for mitochondria.bioRxiv : the preprint server for biology · 2025Article
- Molecular Motors in Blood-Brain Barrier Maintenance by Astrocytes.Brain sciences · 2025Review
- Glycogen synthase kinase 3 (GSK3) inhibition: a potential therapeutic strategy for Alzheimer's disease.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- The lemur tail kinase family in neuronal function and disfunction in neurodegenerative diseases.Cellular and molecular life sciences : CMLS · 2024Review
- Changes in mitochondrial distribution occur at the axon initial segment in association with neurodegeneration in Drosophila.Biology open · 2024Article
- GSK3: A potential target and pending issues for treatment of Alzheimer's disease.CNS neuroscience & therapeutics · 2024Review
- Latest assessment methods for mitochondrial homeostasis in cognitive diseases.Neural regeneration research · 2024Review
- Changes in mitochondrial distribution occur at the axon initial segment in association with neurodegeneration inbioRxiv : the preprint server for biology · 2024Article
- Article
- Glycogen synthase kinase 3β (GSK3β) and presenilin (PS) are key regulators of kinesin-1-mediated cargo motility within axons.Frontiers in cell and developmental biology · 2023Review
- The Link between Oxidative Stress, Mitochondrial Dysfunction and Neuroinflammation in the Pathophysiology of Alzheimer's Disease: Therapeutic Implications and Future Perspectives.Antioxidants (Basel, Switzerland) · 2022Review
- Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer's Disease.Biomedicines · 2022Article
- Programming axonal mitochondrial maintenance and bioenergetics in neurodegeneration and regeneration.Neuron · 2022Review
- Mechanisms associated with the dysregulation of mitochondrial function due to lead exposure and possible implications on the development of Alzheimer's disease.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2022Review
- Editorial: Current Concept and Translational Study in ALS-FTD Spectrum: From Genetics, Neuroinflammation to Neurodegeneration.Frontiers in molecular neuroscience · 2022Article
89 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Several lines of evidence indicate that alterations in axonal transport play a critical role in Alzheimer's disease (AD) neuropathology, but the molecular mechanisms that control this process are not understood fully. Recent work indicates that presenilin 1 (PS1) interacts with glycogen synthase kinase 3beta (GSK3beta). In vivo, GSK3beta phosphorylates kinesin light chains (KLC) and causes the release of kinesin-I from membrane-bound organelles (MBOs), leading to a reduction in kinesin-I driven motility (Morfini et al., 2002b). To characterize a potential role for PS1 in the regulation of kinesin-based axonal transport, we used PS1-/- and PS1 knock-inM146V (KIM146V) mice and cultured cells. We show that relative levels of GSK3beta activity were increased in cells either in the presence of mutant PS1 or in the absence of PS1 (PS1-/-). Concomitant with increased GSK3beta activity, relative levels of KLC phosphorylation were increased, and the amount of kinesin-I bound to MBOs was reduced. Consistent with a deficit in kinesin-I-mediated fast axonal transport, densities of synaptophysin- and syntaxin-I-containing vesicles and mitochondria were reduced in neuritic processes of KIM146V hippocampal neurons. Similarly, we found reduced levels of PS1, amyloid precursor protein, and synaptophysin in sciatic nerves of KIM146V mice. Thus PS1 appears to modulate GSK3beta activity and the release of kinesin-I from MBOs at sites of vesicle delivery and membrane insertion. These findings suggest that mutations in PS1 may compromise neuronal function by affecting GSK-3 activity and kinesin-I-based motility.
Indexed as
Identifiers
12805290PMC6740780W1869318026What 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.