ArticleCell death & disease2021
Rab35 and glucocorticoids regulate APP and BACE1 trafficking to modulate Aβ production.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Neurodegenerative NMNAT2 Deficiency Promotes APP Processing in a SARM1-Dependent Manner.Cells · 2026Article
- Electroacupuncture reduces amyloid beta accumulation and improves cerebral ischemia-induced cognitive impairment in a N6-methyladenosine-dependent manner.Journal of molecular histology · 2026Article
- Neuroinflammatory stress preferentially impacts synaptic MAPK signaling and mitochondria in excitatory neurons.Molecular neurodegeneration advances · 2026Article
- The embedding of stress: mitophagy as a mechanism for the central nervous system (CNS) programming and lifelong disease vulnerability.Frontiers in cell and developmental biology · 2026Review
- Glucocorticoids regulate small extracellular vesicle (sEV) release via activation of nSMase2.bioRxiv : the preprint server for biology · 2025Article
- Dysregulation of Inositol Polyphosphate 5-Phosphatase OCRL in Alzheimer's Disease: Implications for Autophagy Dysfunction.International journal of molecular sciences · 2025Article
- The role of small GTPases in Alzheimer's disease tau pathologies.Frontiers in cellular neuroscience · 2025Review
- The multiple roles of chronic stress and glucocorticoids in Alzheimer's disease pathogenesis.Trends in neurosciences · 2024Review
- Proteostasis and neurodegeneration: a closer look at autophagy in Alzheimer's disease.Frontiers in aging neuroscience · 2023Review
- Involvement of brain-derived neurotrophic factor signaling in the pathogenesis of stress-related brain diseases.Frontiers in molecular neuroscience · 2023Review
- Article
- SPIN90 Deficiency Ameliorates Amyloid β Accumulation by Regulating APP Trafficking in AD Model Mice.International journal of molecular sciences · 2022Article
- Lipopolysaccharide-Induced Model of Neuroinflammation: Mechanisms of Action, Research Application and Future Directions for Its Use.Molecules (Basel, Switzerland) · 2022Review
- Roles of traditional chinese medicine regulating neuroendocrinology on AD treatment.Frontiers in endocrinology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Chronic stress and elevated glucocorticoids (GCs), the major stress hormones, are risk factors for Alzheimer's disease (AD) and promote AD pathomechanisms, including overproduction of toxic amyloid-β (Aβ) peptides and intraneuronal accumulation of hyperphosphorylated Tau protein. The latter is linked to downregulation of the small GTPase Rab35, which mediates Tau degradation via the endolysosomal pathway. Whether Rab35 is also involved in Aβ overproduction remains an open question. Here, we find that hippocampal Rab35 levels are decreased not only by stress/GC but also by aging, another AD risk factor. Moreover, we show that Rab35 negatively regulates Aβ production by sorting amyloid precursor protein (APP) and β-secretase (BACE1) out of the endosomal network, where they interact to produce Aβ. Interestingly, Rab35 coordinates distinct intracellular trafficking steps for BACE1 and APP, mediated by its effectors OCRL and ACAP2, respectively. Finally, we demonstrate that Rab35 overexpression prevents the amyloidogenic trafficking of APP and BACE1 induced by high GC levels. These studies identify Rab35 as a key regulator of APP processing and suggest that its downregulation may contribute to stress-related and AD-related amyloidogenesis.
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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.