ReviewAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Tau degradation in Alzheimer's disease: Mechanisms and therapeutic opportunities.
Review 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 28 papers.
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Who cites it
28 citing papers in PubMed.
- TRIM28 SUMOylates IRF3 in astrocytes to drive neutrophils infiltration and ischemic cerebral injury.Cell death and differentiation · 2026Article
- Distinct single-nucleus RNA-seq changes among non-neuronal cells in ADNC, LATE-NC, and mixed pathologies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Tuberostemonine ameliorates Alzheimer's disease pathology by suppression of the p38 MAPK signaling pathway.iScience · 2026Article
- Tau dysfunction in alzheimer's disease: molecular and cellular mechanisms, genetic modulation, and therapeutic perspectives.Molecular biology reports · 2026Review
- Domain-dependent uncoupling of the co-chaperone and E3 ubiquitin ligase CHIP underlies heterogeneity in spinocerebellar ataxia 48.The Journal of biological chemistry · 2026Article
- MINERVA: a public XAI-powered platform advancing multi-target discovery in Alzheimer's disease.Journal of cheminformatics · 2026Article
- Tau368 improves p-tau diagnostic accuracy for FTLD-tau from FTLD-TDP.Acta neuropathologica · 2026Article
- Meningeal lymphatic dysfunction in Alzheimer's disease: molecular mechanisms, clinical implications, and future perspectives.Molecular neurodegeneration · 2026Review
- Histone modification dynamics in brain aging: unlocking therapeutic potential.Cell death & disease · 2026Review
- Molecular engineering of lysosome-based degraders unveils a rapidly expanding therapeutic strategy.Autophagy · 2026Review
- PROTAC-mediated multi-target protein degradation in Alzheimer's disease: mechanistic insights, therapeutic applications, and translational challenges.RSC medicinal chemistry · 2026Review
- Novel Small-Molecule Analogues of IU1 Ameliorate Amyloid-β Mediated Toxicity in Alzheimer's Disease Cell and Worm Models.International journal of molecular sciences · 2026Article
- Review
- Proteasome 20S beta 8 (PSMB8) as a metabolic switcher of neuronal ferroptosis in multiple sclerosis.Cell death and differentiation · 2026Article
- Overcoming the blood-brain barrier in Alzheimer's disease: translational perspectives on advanced drug delivery platforms.Frontiers in neuroscience · 2026Review
- From seeds to symptoms: the molecular landscape of tau seeding in Alzheimer's disease.Frontiers in neuroscience · 2026Review
- Loss of CAMKK2 and iron-transport proteins-transferrin and its receptor-in the Alzheimer's disease hippocampus: link to tau pathology.Frontiers in cell and developmental biology · 2026Article
- Protein lactylation in Alzheimer's disease: bridging metabolism, pathology, and therapeutic opportunity.Frontiers in aging neuroscience · 2026Review
- Hyaluronic acid: emerging roles and biomaterial innovations in Alzheimer's and Parkinson's disease therapy.Frontiers in pharmacology · 2026Review
- Integrating network pharmacology and experimental validation strategies to investigate the mechanisms and key flavonoids in medicinal and edible citrus plants against Alzheimer's disease.Frontiers in aging neuroscience · 2026Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
In Alzheimer's disease (AD), tau undergoes abnormal post-translational modifications and aggregations. Impaired intracellular degradation pathways further exacerbate the accumulation of pathological tau. A new strategy - targeted protein degradation - recently emerged as a modality in drug discovery where bifunctional molecules bring the target protein close to the degradation machinery to promote clearance. Since 2016, this strategy has been applied to tau pathologies and attracted broad interest in academia and the pharmaceutical industry. However, a systematic review of recent studies on tau degradation mechanisms is lacking. Here we review tau degradation mechanisms (the ubiquitin-proteasome system and the autophagy-lysosome pathway), their dysfunction in AD, and tau-targeted degraders, such as proteolysis-targeting chimeras and autophagy-targeting chimeras. We emphasize the need for a continuous exploration of tau degradation mechanisms and provide a future perspective for developing tau-targeted degraders, encouraging researchers to work on new treatment options for AD patients. HIGHLIGHTS: Post-translational modifications, aggregation, and mutations affect tau degradation. A vicious circle exists between impaired degradation pathways and tau pathologies. Ubiquitin plays an important role in complex degradation pathways. Tau-targeted degraders provide promising strategies for novel AD treatment.
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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.