BAG1 Overexpression Stabilizes High Molecular Tau Protein – a Crucial Role of the Co-chaperone in Tau Pathology Article Swipe
Sandra C. Signore
,
Fred S. Wouters
,
Matthias Schmitz
,
Mathias Baehr
,
Pawel Kermer
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.11648/j.ajpn.20210902.18
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.11648/j.ajpn.20210902.18
The Bcl-2-associated athanogene-1 (BAG1) exerts neuroprotective properties which has been shown in several studies of neurodegenerative disease models like Parkinson’s disease, Huntington’s disease and even cerebral ischemia. On the basis of the well-known neuroprotective function of the co-chaperone, we wanted to examine its properties in a model for Alzheimer’s disease, a neurological disorder of great significance. One of the hallmarks of Alzheimer’s disease, besides extracellular plaque formation, is the intra-neuronal accumulation of hyper-phosphorylated tau protein that leads to tau aggregation. When overexpressed together with a tau mutant with high propensity for aggregation, BAG1 led to the stabilization of high-molecular tau fragments in rat CSM 14.1 cells compared to wild-type cells. Deletion of the domain in BAG1 that is responsible for binding to Hsp70 (BAGΔC) abolished this effect, which could be confirmed by immunocytochemistry. In fact, BAG1 does not only increase mutant tau aggregation but also prevents its degradation by the proteasome. Immunochemistry revealed that overexpression of the Bcl-2-associated athanogene-1 gives rise to large tau aggregates surrounded by lysosomes. Furthermore, toxicity assays indicated increased tau toxicity in BAG1 overexpressing cells. Hence, in contrast to other neurodegenerative diseases, BAG1 seems to enhance Alzheimer´s pathology and to promote cell death due to the stabilization of aggregation-prone tau species that evade proteasomal clearance. To conclude, this analysis provides a new sight of the co-chaperone BAG1 and yet again demonstrates its complex influence in a model of Alzheimer’s disease.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.11648/j.ajpn.20210902.18
- http://article.sciencepublishinggroup.com/pdf/10.11648.j.ajpn.20210902.18.pdf
- OA Status
- diamond
- Cited By
- 3
- References
- 38
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3174210368
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- OpenAlex ID
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https://openalex.org/W3174210368Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.11648/j.ajpn.20210902.18Digital Object Identifier
- Title
-
BAG1 Overexpression Stabilizes High Molecular Tau Protein – a Crucial Role of the Co-chaperone in Tau PathologyWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-01-01Full publication date if available
- Authors
-
Sandra C. Signore, Fred S. Wouters, Matthias Schmitz, Mathias Baehr, Pawel KermerList of authors in order
- Landing page
-
https://doi.org/10.11648/j.ajpn.20210902.18Publisher landing page
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https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajpn.20210902.18.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
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-
diamondOpen access status per OpenAlex
- OA URL
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https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajpn.20210902.18.pdfDirect OA link when available
- Concepts
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Neuroprotection, Chaperone (clinical), Cell biology, Tauopathy, Protein aggregation, Tau protein, Neurodegeneration, Biology, Immunocytochemistry, Extracellular, Mutant, Alzheimer's disease, Chemistry, Neuroscience, Disease, Pathology, Medicine, Biochemistry, Endocrinology, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
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3Total citation count in OpenAlex
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2025: 1, 2022: 2Per-year citation counts (last 5 years)
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38Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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