ArticleHuman molecular genetics2013
Presenilin controls kinesin-1 and dynein function during APP-vesicle transport in vivo.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
42 citing papers in PubMed, 63 citations in OpenAlex.
- Therapeutic Advances in Targeting the Amyloid-β Pathway for Alzheimer's Disease.Brain sciences · 2025Review
- Opposing roles for GSK3β and ERK1-dependent phosphorylation of huntingtin during neuronal dysfunction and cell death in Huntington's disease.Cell death & disease · 2025Article
- Genetic evidence for a functional association between Parkinson's disease proteins leucine-rich repeat kinase 2 andFrontiers in molecular neuroscience · 2025Article
- Clinical trials of new drugs for Alzheimer disease: a 2020-2023 update.Journal of biomedical science · 2023Review
- Article
- HTT (huntingtin) and RAB7 co-migrate retrogradely on a signaling LAMP1-containing late endosome during axonal injury.Autophagy · 2023Article
- 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
- Short-Term and Long-Term Sensitization Differentially Alters the Composition of an Anterograde Transport Complex ineNeuro · 2023Article
- APP accumulates with presynaptic proteins around amyloid plaques: A role for presynaptic mechanisms in Alzheimer's disease?Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Article
- Quantum-dot-labeled synuclein seed assay identifies drugs modulating the experimental prion-like transmission.Communications biology · 2022Article
- A stop or go switch: glycogen synthase kinase 3β phosphorylation of the kinesin 1 motor domain at Ser314 halts motility without detaching from microtubules.Development (Cambridge, England) · 2021Article
- Differential mitochondrial roles for α-synuclein in DRP1-dependent fission and PINK1/Parkin-mediated oxidation.Cell death & disease · 2021Article
- The plasma peptides of Alzheimer's disease.Clinical proteomics · 2021Article
- Excess Rab4 rescues synaptic and behavioral dysfunction caused by defective HTT-Rab4 axonal transport in Huntington's disease.Acta neuropathologica communications · 2020Article
- Clinical trials of new drugs for Alzheimer disease.Journal of biomedical science · 2020Review
- Whole-Brain Three-Dimensional Profiling Reveals Brain Region Specific Axon Vulnerability in 5xFAD Mouse Model.Frontiers in neuroanatomy · 2020Article
- Excess active P13K rescues huntingtin-mediated neuronal cell death but has no effect on axonal transport defects.Apoptosis : an international journal on programmed cell death · 2019Article
- The Non-amyloidal Component Region of α-Synuclein Is Important for α-Synuclein Transport Within Axons.Frontiers in cellular neuroscience · 2019Article
- A Role forFrontiers in cellular neuroscience · 2019Article
- The presenilin loop region is essential for glycogen synthase kinase 3 β (GSK3β) mediated functions on motor proteins during axonal transport.Human molecular genetics · 2018Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Neurons and other cells require intracellular transport of essential components for viability and function. Previous work has shown that while net amyloid precursor protein (APP) transport is generally anterograde, individual vesicles containing APP move bi-directionally. This discrepancy highlights our poor understanding of the in vivo regulation of APP-vesicle transport. Here, we show that reduction of presenilin (PS) or suppression of gamma-secretase activity substantially increases anterograde and retrograde velocities for APP vesicles. Strikingly, PS deficiency has no effect on an unrelated cargo vesicle class containing synaptotagmin, which is powered by a different kinesin motor. Increased velocities caused by PS or gamma-secretase reduction require functional kinesin-1 and dynein motors. Together, our findings suggest that a normal function of PS is to repress kinesin-1 and dynein motor activity during axonal transport of APP vesicles. Furthermore, our data suggest that axonal transport defects induced by loss of PS-mediated regulatory effects on APP-vesicle motility could be a major cause of neuronal and synaptic defects observed in Alzheimer's Disease (AD) pathogenesis. Thus, perturbations of APP/PS transport could contribute to early neuropathology observed in AD, and highlight a potential novel therapeutic pathway for early intervention, prior to neuronal loss and clinical manifestation of disease.
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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.