ArticleNature cell biology2025
Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer's disease.
Article in Nature cell biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed.
- Autophagy Flux Is Remodeled Sex- and Cell Type-Specifically During Human Aging, and Is Linked to Reduced Physical Function in Older Adults.Aging cell · 2026Article
- From aggregate structure to disease trajectory: the role of the proteostasis network.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
- Lysosomes enlist endoplasmic reticulum microdomains for repair.Nature cell biology · 2026Article
- Hippocampal neural stem cell-derived extracellular vesicles modulate microglia to promote resilience against tau oligomers.Neural regeneration research · 2026Article
- Proteostasis of organelles in aging and disease.The FEBS journal · 2026Review
- Roles of autophagy in brain homeostasis and disease.Nature neuroscience · 2026Review
- Astrocytes mobilize a broader repertoire of lysosomal repair mechanisms than neurons.iScience · 2026Article
- Advancing a systems-level understanding of neurodegeneration: the BrightFocus Alzheimer's disease research portfolio.Molecular neurodegeneration · 2026Article
- Alzheimer's Disease as a Multi-Layer Network Disorder: A Systems Biology Framework Integrating Multi-Omics Mechanisms.Biomedicines · 2026Review
- Article
- Lysosomes and lysosomal dysfunction in ageing biology.Nature cell biology · 2026Review
- Global cellular responses to lysosomal damage.Current biology : CB · 2026Review
- Age-associated decline of Lamtor5 drives immunosenescence and systemic aging via cGAS-mediated paracrine inflammation.Cell death and differentiation · 2026Article
- Zinc-mediated lysosomal activation by 1H10 enhances autophagy and attenuates tau pathology in Alzheimer's disease models.Molecular brain · 2026Article
- The C9orf72/SMCR8 complex maintains microglial homeostasis via RAB8A-ESCRT-mediated lysosomal repair.The EMBO journal · 2026Article
- Immune cell-specific genetic architecture of Alzheimer's disease revealed by multi-omics analysis for therapeutic target discovery and prioritization.Translational psychiatry · 2026Article
- Three-dimensional direct neuronal reprogramming for modeling Alzheimer's disease neuropathology.Nature protocols · 2026Review
- Investigating the Causal Links between the Aging Process and Alzheimer's Disease Pathogenesis.International journal of stem cells · 2026Review
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15 authors.
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Abstract
Ageing is the most prominent risk factor for Alzheimer's disease (AD). However, the cellular mechanisms linking neuronal proteostasis decline to the characteristic aberrant protein deposits in the brains of patients with AD remain elusive. Here we develop transdifferentiated neurons (tNeurons) from human dermal fibroblasts as a neuronal model that retains ageing hallmarks and exhibits AD-linked vulnerabilities. Remarkably, AD tNeurons accumulate proteotoxic deposits, including phospho-tau and amyloid β, resembling those in APP mouse brains and the brains of patients with AD. Quantitative tNeuron proteomics identify ageing- and AD-linked deficits in proteostasis and organelle homeostasis, most notably in endosome-lysosomal components. Lysosomal deficits in aged tNeurons, including constitutive lysosomal damage and ESCRT-mediated lysosomal repair defects, are exacerbated in AD tNeurons and linked to inflammatory cytokine secretion and cell death. Providing support for the centrality of lysosomal deficits in AD, compounds ameliorating lysosomal function reduce amyloid β deposits and cytokine secretion. Thus, the tNeuron model system reveals impaired lysosomal homeostasis as an early event of ageing and AD.
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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.