ArticleCell reports2020
Endosomal Dysfunction Induced by Directly Overactivating Rab5 Recapitulates Prodromal and Neurodegenerative Features of Alzheimer's Disease.
Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 126 citations in OpenAlex.
- Preclinical and randomized clinical evaluation of the p38α kinase inhibitor neflamapimod for basal forebrain cholinergic degeneration.Nature communications · 2022Trial
- Integrating CSF and EV Proteomes Enhances Biomarker Discovery by Capturing Shared Variation Across Compartments.bioRxiv : the preprint server for biology · 2026Article
- Co-activation of Selective Nicotinic Acetylcholine Receptor Subtypes Is Required for Neuroprotection against Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Local translation of endosome-associated lc3b mRNA in axons contributes to endosomal clearance.EMBO reports · 2026Article
- Rab5 hyperactivation: The central hub for endolysosomal dysfunction in Down syndrome.Neural regeneration research · 2026Article
- SORL1 variant links endosomal amyloid precursor protein mis-sorting to axonal transport defects and neuronal dysfunction.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Molecular architects of memory: BDNF/TrkB signaling and trafficking in neuronal plasticity and memory.Molecular psychiatry · 2026Review
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- Endosome maturation is orchestrated by inside-out proton signaling through a NaNature communications · 2026Article
- Rab5 nucleotide binding promotes oxidative metabolism to fuel hepatocellular carcinoma cell proliferation.The Journal of biological chemistry · 2026Article
- A Multi-Network Approach Identifies Proteins Related to Dendritic Spines in Alzheimer's Disease.eNeuro · 2026Article
- Functional Analysis of Late-Onset Alzheimer's Disease Risk Genes inbioRxiv : the preprint server for biology · 2026Article
- Axonopathy: mechanisms and potential therapeutic targets for neurodegenerative diseases.Translational neurodegeneration · 2026Review
- Impaired BDNF-TrkB trafficking and signalling in Down syndrome basal forebrain neurons.Cell death & disease · 2026Article
- Endosome maturation is orchestrated by inside-out proton signaling through a NaResearch square · 2026Article
- Article
- Molecular mechanism of Alzheimer's disease using integrated multi-omics.Frontiers in aging neuroscience · 2026Review
- Proteomic analysis links truncated tau to lysosome motility, autophagy, and endo-lysosomal dysfunction.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Article
- Discoidin, CUB and LCCL domain containing 2 modulates angiogenesis by inhibiting VEGF receptor 2 endocytosis in endothelial cells.Journal of molecular medicine (Berlin, Germany) · 2025Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Neuronal endosomal dysfunction, the earliest known pathobiology specific to Alzheimer's disease (AD), is mediated by the aberrant activation of Rab5 triggered by APP-β secretase cleaved C-terminal fragment (APP-βCTF). To distinguish pathophysiological consequences specific to overactivated Rab5 itself, we activate Rab5 independently from APP-βCTF in the PA-Rab5 mouse model. We report that Rab5 overactivation alone recapitulates diverse prodromal and degenerative features of AD. Modest neuron-specific transgenic Rab5 expression inducing hyperactivation of Rab5 comparable to that in AD brain reproduces AD-related Rab5-endosomal enlargement and mistrafficking, hippocampal synaptic plasticity deficits via accelerated AMPAR endocytosis and dendritic spine loss, and tau hyperphosphorylation via activated glycogen synthase kinase-3β. Importantly, Rab5-mediated endosomal dysfunction induces progressive cholinergic neurodegeneration and impairs hippocampal-dependent memory. Aberrant neuronal Rab5-endosome signaling, therefore, drives a pathogenic cascade distinct from β-amyloid-related neurotoxicity, which includes prodromal and neurodegenerative features of AD, and suggests Rab5 overactivation as a potential therapeutic target.
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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.