ArticleAutophagy2019
BAG3 and SYNPO (synaptopodin) facilitate phospho-MAPT/Tau degradation via autophagy in neuronal processes.
Article in Autophagy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 99 citations in OpenAlex.
- Fractionated proteomics identifies a protein network mitigating resistance exercise-induced damage in human skeletal muscle.Nature communications · 2026Article
- CSF microtubule-associated protein 1 light chain 3A and 3B levels are associated with tau pathology and Alzheimer's disease risk through amyloid deposition and microglial signaling.Journal of neuroinflammation · 2026Article
- Neonatal propofol exposure impairs synaptic plasticity and cognition, associated with BAG3 upregulation and disrupted synaptic protein homeostasis.Frontiers in neuroscience · 2026Article
- Bipolar and schizophrenia risk gene AKAP11 encodes an autophagy receptor coupling the regulation of PKA kinase network homeostasis to synaptic transmission.Nature communications · 2025Article
- Metabolic functions for molecular chaperones and stress proteins in microcephaly.Cellular and molecular life sciences : CMLS · 2025Review
- Peripartum sertraline impacts maternal neurobehavioral and neurodegenerative mechanisms in pregnant and postpartum mice.Molecular psychiatry · 2025Article
- The connection between autophagy and Alzheimer's disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Genetic and proteomic analysis identifies BAG3 as an amyloid-responsive regulator of neuronal proteostasis.Acta neuropathologica · 2025Article
- REV-ERBα regulates brain NADNature aging · 2025Article
- One BAG Does Not Fit All: Differences and Similarities of BAG Family Members in Mediating Central Nervous System Homeostasis.Biological psychiatry · 2025Review
- Bone marrow mesenchymal stem cells alleviate neurological dysfunction by reducing autophagy damage via downregulation of SYNPO2 in neonatal hypoxic-ischemic encephalopathy rats.Cell death & disease · 2025Article
- Investigating the Therapeutic Mechanisms of Total Saikosaponins in Alzheimer's Disease: A Metabolomic and Proteomic Approach.Pharmaceuticals (Basel, Switzerland) · 2025Article
- A systematic review of associations between the environment, DNA methylation, and cognition.Environmental epigenetics · 2025Review
- Genome-wide association neural networks identify genes linked to family history of Alzheimer's disease.Briefings in bioinformatics · 2024Article
- 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
- BAG3 regulates the specificity of the recognition of specific MAPT species by NBR1 and SQSTM1.Autophagy · 2024Article
- The NDR family of kinases: essential regulators of aging.Frontiers in molecular neuroscience · 2024Review
- Untangling Tau: Molecular Insights into Neuroinflammation, Pathophysiology, and Emerging Immunotherapies.Current issues in molecular biology · 2023Review
- Synaptopodin-2: a potential tumor suppressor.Cancer cell international · 2023Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
A major cellular catabolic pathway in neurons is macroautophagy/autophagy, through which misfolded or aggregation-prone proteins are sequestered into autophagosomes that fuse with lysosomes, and are degraded. MAPT (microtubule-associated protein tau) is one of the protein clients of autophagy. Given that accumulation of hyperphosphorylated MAPT contributes to the pathogenesis of Alzheimer disease and other tauopathies, decreasing endogenous MAPT levels has been shown to be beneficial to neuronal health in models of these diseases. A previous study demonstrated that the HSPA/HSP70 co-chaperone BAG3 (BCL2-associated athanogene 3) facilitates endogenous MAPT clearance through autophagy. These findings prompted us to further investigate the mechanisms underlying BAG3-mediated autophagy in the degradation of endogenous MAPT. Here we demonstrate for the first time that BAG3 plays an important role in autophagic flux in the neurites of mature neurons (20-24 days in vitro [DIV]) through interaction with the post-synaptic cytoskeleton protein SYNPO (synaptopodin). Loss of either BAG3 or SYNPO impeded the fusion of autophagosomes and lysosomes predominantly in the post-synaptic compartment. A block of autophagy leads to accumulation of the autophagic receptor protein SQSTM1/p62 (sequestosome 1) as well as MAPT phosphorylated at Ser262 (p-Ser262). Furthermore, p-Ser262 appears to accumulate in autophagosomes at post-synaptic densities. Overall these data provide evidence of a novel role for the co-chaperone BAG3 in synapses. In cooperation with SYNPO, it functions as part of a surveillance complex that facilitates the autophagic clearance of MAPT p-Ser262, and possibly other MAPT species at the post-synapse. This appears to be crucial for the maintenance of a healthy, functional synapse.
Indexed as
Identifiers
What OpenQuestion holds
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.