ArticleNature aging2025
Subcellular proteomics and iPSC modeling uncover reversible mechanisms of axonal pathology in Alzheimer's disease.
Article in Nature aging, 2025. 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.
- Astrocytes viewed through the lens of their proteomes and subproteomes.Nature reviews. Neuroscience · 2026Review
- RNA acetylation modification ac4C: An emerging regulatory hub of RNA metabolism disruption in Alzheimer's disease.Molecular biology reports · 2026Review
- Neuronal overexpression of Nrf2 reduces dystrophic neurites in 5XFAD Alzheimer's disease model mice.Alzheimer's research & therapy · 2026Article
- The presynaptic protein bassoon is a biofluid biomarker of synaptic pathology in multiple sclerosis.EBioMedicine · 2026Article
- A Question of Origins: Non-neuronal Sources of Amyloid-β.Neuroscience bulletin · 2026Review
- Dexter Energy Transfer Photocatalytic Microdissection of Amyloid Plaques in Alzheimer's Disease.JACS Au · 2026Article
- Proximity labeling in neuroscience: decoding molecular landscapes for precision neurology.Translational neurodegeneration · 2026Review
- The therapeutic potential of botanicals: how medicinal plants targeting autophagy can reverse metabolic-associated fatty liver disease.Frontiers in pharmacology · 2026Review
- Non-Vesicular Extracellular Particle (NVEP) Proteomes from Diverse Biological Sources Reveal Specific Marker Composition with Varying Enrichment Levels.Biomolecules · 2025Article
- Neuronal branching in stem cell models of mitochondrial and neurological diseases.Stem cells (Dayton, Ohio) · 2025Review
- Pathological Calcium Signaling in Traumatic Brain Injury and Alzheimer's Disease: From Acute Neuronal Injury to Chronic Neurodegeneration.International journal of molecular sciences · 2025Review
- An integrated view of the relationships between amyloid, tau, and inflammatory pathophysiology in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Myelin-axon interface vulnerability in Alzheimer's disease revealed by subcellular proteomics and imaging of human and mouse brain.Nature neuroscience · 2025Article
- FGF-Mediated Axon Guidance: Role of Downstream Signaling Pathways in Cytoskeletal Control.Cells · 2025Review
Corrections and comments
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Authors and funding
22 authors.
Funding
Abstract
Dystrophic neurites (also termed axonal spheroids) are found around amyloid deposits in Alzheimer's disease (AD), where they impair axonal electrical conduction, disrupt neural circuits and correlate with AD severity. Despite their importance, the mechanisms underlying spheroid formation remain incompletely understood. To address this, we developed a proximity labeling approach to uncover the proteome of spheroids in human postmortem and mouse brains. Additionally, we established a human induced pluripotent stem cell (iPSC)-derived AD model enabling mechanistic investigation and optical electrophysiology. These complementary approaches revealed the subcellular molecular architecture of spheroids and identified abnormalities in key biological processes, including protein turnover, cytoskeleton dynamics and lipid transport. Notably, the PI3K/AKT/mTOR pathway, which regulates these processes, was activated in spheroids. Furthermore, phosphorylated mTOR levels in spheroids correlated with AD severity in humans. Notably, mTOR inhibition in iPSC-derived neurons and mice ameliorated spheroid pathology. Altogether, our study provides a multidisciplinary toolkit for investigating mechanisms and therapeutic targets for axonal pathology in neurodegeneration.
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