ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
TMEM59 deficiency activates chaperone-mediated autophagy and ameliorates disease-like pathologies in tauopathy model mice.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- TMEM59 regulates microglial Aβ phagocytosis in a TREM2-dependent manner and acts as a potential therapeutic target for Aβ amyloidosis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- CRISPR/Cas9 loss-of-function screen in a neuronal model of AP-4 deficiency identifies ATG9A trafficking modulators.JCI insight · 2026Article
- Acetylation Regulates ACSL4 Degradation Through Chaperone-Mediated Autophagy to Alleviate Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026Review
- TMEM59 deficiency activates chaperone-mediated autophagy and ameliorates disease-like pathologies in tauopathy model mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
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Authors and funding
13 authors.
Funding
Abstract
introductionTauopathy is characterized by the pathology of tau deposits in the brain. Transmembrane protein 59 (TMEM59) is correlated with Alzheimer's disease (AD), the most common type of tauopathy. However, whether and how TMEM59 regulates tau pathology remains unknown.
methodsWe analyzed TMEM59 levels in the brains of AD patients and the tau
resultsTMEM59 levels increased in the brains of AD patients and PS19 mice at pathological stages. TMEM59 haploinsufficiency attenuated cognitive deficits and disease-related pathologies in PS19 mice. TMEM59 deficiency promoted lysosome-associated membrane protein type 2A levels and CMA activity, whereas TMEM59 overexpression had the opposite effects. DISCUSSION: Our study identifies an important role of TMEM59 in regulating CMA and reveals the potential of targeting TMEM59 for tauopathy intervention. HIGHLIGHTS: Transmembrane protein 59 (TMEM59) levels increase in the brains of Alzheimer's disease patients and the tau
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