Calpain-Mediated Tau Cleavage: A Mechanism Leading to Neurodegeneration Shared by Multiple Tauopathies
Open accessAbstract
Tau dysfunction has been associated with a host of neurodegenerative diseases called tauopathies. These diseases share, as a common pathological hallmark, the presence of intracellular aggregates of hyperphosphorylated tau in affected brain areas. Aside from tau hyperphosphorylation, little is known about the role of other posttranslational modifications in tauopathies. Recently, we obtained data suggesting that calpain-mediated tau cleavage leading to the generation of a neurotoxic tau fragment might play an important role in Alzheimer's disease. In the current study, we assessed the presence of this tau fragment in several tauopathies. Our results show high levels of the 17-kDa tau fragment and enhanced calpain activity in the temporal cortex of AD patients and in brain samples obtained from patients with other tauopathies. In addition, our data suggest that this fragment could partially inhibit tau aggregation. Conversely, tau aggregation might prevent calpain-mediated cleavage, establishing a feedback circuit that might lead to the accumulation of this toxic tau fragment. Collectively, these data suggest that the mechanism underlying the generation of the 17-kDa neurotoxic tau fragment might be part of a conserved pathologic process shared by multiple tauopathies.
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Elevated tau243-441 levels are observed in the tau transgenic Tg601 mouse model.
“while elevated tau243–441 levels are observed in the tau transgenic Tg601 mouse model [207, 208].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [208]
Increased calpain activity and levels of tau45-230 have been identified in brain samples from AD and several other tauopathies.
“Increased calpain activity and levels of tau45–230 has been identified in brain samples from AD and several other tauopathies”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [208]
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- Authors
- Ferreira, A., & Bigio, E. H.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Ferreira, Adriana
- Venue
- Molecular Medicine
- Published
- 2011-03-21
- Volume
- 17
- Issue
- 7-8
- Pages
- 676-685
- ISSN
- 1076-1551 (ISSN-L)
- 1528-3658
- PMC
- PMC3146621
- OpenAlex
- W104689190
- Cited by
- 112
- References
- 65
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 3 · 2023: 8 · 2022: 6 · 2021: 1 · 2020: 11 · 2019: 12 · 2018: 12 · 2017: 9 · 2016: 9 · 2015: 8 · 2014: 5 · 2013: 8 · 2012: 8
- FWCI
- 5.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Molecular Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chicago Community Trust
- Chicago Biomedical Consortium
- National Institutes of Health
- National Institute on Aging (P30AG13854, P30AG013854)
- National Institute of Neurological Disorders and Stroke (R01NS039080, R01 NS39080)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Calpain Protease Function and Regulation
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- calpain, tau cleavage, tauopathy, Alzheimer's disease, tau aggregation, hyperphosphorylated tau, post-translational modification, temporal cortex, neurodegeneration
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Animals, Calpain, Cells, Cultured, Cerebral Cortex, Female, Humans, Male, Microscopy, Electron, Middle Aged, Molecular Weight, Neurons, Phosphorylation, Immunoblotting, Gene Expression, Neurofibrillary Tangles, tau Proteins, Neurodegenerative Diseases, Reverse Transcriptase Polymerase Chain Reaction, Tauopathies, Rats, Primary Cell Culture
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