ArticleNeurobiology of aging2015
BAG3 facilitates the clearance of endogenous tau in primary neurons.
Article in Neurobiology of aging, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 105 citations in OpenAlex.
- Neuroproteasomes regulate endogenous tau paired helical filament formation in an APOE genotype- and age-dependent manner.Nature neuroscience · 2026Article
- Small bites for big problems: stepwise aggregate degradation by autophagy.Biochemical Society transactions · 2026Review
- BAG3 modulates clathrin-mediated endocytosis and tau uptake in astrocytes.American journal of physiology. Cell physiology · 2026Article
- circPDE4B downregulation triggers GEMIN5‑dependent translational stress response and autophagy to reduce MAPT pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Depletion of BIS in astrocytes aggravates reactive gliosis following photothrombotic brain injury.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- Integration of aged brain multi-omics reveals cross-system mechanisms underlying Alzheimer's disease heterogeneity.Cell reports · 2026Article
- A Bioinformatic Analysis of BAG Protein Interactors and Pathways in Alzheimer's and Parkinson's Disease.Journal of molecular neuroscience : MN · 2026Review
- Dual targeting of the UPS and autophagy as a novel therapy for neurodegenerative proteinopathies.Frontiers in cellular neuroscience · 2026Review
- The modifier matrix: emerging roles of ubiquitin-like proteins in Alzheimer's disease.Molecular neurodegeneration advances · 2026Review
- Heat shock proteins (Hsp70 and Hsp90) in neurodegeneration: pathogenic roles and therapeutic potential.Frontiers in aging neuroscience · 2026Review
- BAG3 modulates clathrin-mediated endocytosis and tau uptake in astrocytes.bioRxiv : the preprint server for biology · 2025Article
- Metabolic functions for molecular chaperones and stress proteins in microcephaly.Cellular and molecular life sciences : CMLS · 2025Review
- Genetic and proteomic analysis identifies BAG3 as an amyloid-responsive regulator of neuronal proteostasis.Acta neuropathologica · 2025Article
- Integration of aged brain multi-omics reveals cross-system mechanisms underlying Alzheimer's disease heterogeneity.bioRxiv : the preprint server for biology · 2025Article
- One BAG Does Not Fit All: Differences and Similarities of BAG Family Members in Mediating Central Nervous System Homeostasis.Biological psychiatry · 2025Review
- Tau degradation in Alzheimer's disease: Mechanisms and therapeutic opportunities.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Identification of phosphatases that dephosphorylate the co-chaperone BAG3.Life science alliance · 2025Article
- Neuronal BAG3 attenuates tau hyperphosphorylation, synaptic dysfunction, and cognitive deficits induced by traumatic brain injury via the regulation of autophagy-lysosome pathway.Acta neuropathologica · 2024Article
- Association between gynecologic cancer and Alzheimer's disease: a bidirectional mendelian randomization study.BMC cancer · 2024Article
- Tau fibrils evade autophagy by excessive p62 coating and TAX1BP1 exclusion.Science advances · 2024Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Tau is a microtubule associated protein that is found primarily in neurons, and in pathologic conditions, such as Alzheimer's disease (AD) it accumulates and contributes to the disease process. Because tau plays a fundamental role in the pathogenesis of AD and other tauopathies, and in AD mouse models reducing tau levels improves outcomes, approaches that facilitate tau clearance are being considered as therapeutic strategies. However, fundamental to the development of such interventions is a clearer understanding of the mechanisms that regulate tau clearance. Here, we report a novel mechanism of tau degradation mediated by the co-chaperone BAG3. BAG3 has been shown to be an essential component of a complex that targets substrates to the autophagy pathway for degradation. In rat primary neurons, activation of autophagy by inhibition of proteasome activity or treatment with trehalose resulted in significant decreases in tau and phospho-tau levels. These treatments also induced an upregulation of BAG3. Proteasome inhibition activated JNK, which was responsible for the upregulation of BAG3 and increased tau clearance. Inhibiting JNK or knocking down BAG3 blocked the proteasome inhibition-induced decreases in tau. Further, BAG3 overexpression alone resulted in significant decreases in tau and phospho-tau levels in neurons. These results indicate that BAG3 plays a critical role in regulating the levels of tau in neurons, and interventions that increase BAG3 levels could provide a therapeutic approach in the treatment of 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.