Cited by 112Alzheimer's disease research and treatmentsCalpain Protease Function and RegulationDementia and Cognitive Impairment Research

Calpain-Mediated Tau Cleavage: A Mechanism Leading to Neurodegeneration Shared by Multiple Tauopathies

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Ferreira, Adriana, Bigio, Eileen H·2011·Molecular Medicine

Abstract

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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  1. Goslin K, Banker GA. (1991) Rat hippocampal neurons in low-density culture. In: Culturing Nerve Cells. Banker G, Goslin K (eds). MIT Press, Cambridge, pp. 251-83.
  2. Grunke-Iqbal I, et al. microtubule-associated pro- tein t (tau) in Alzheimer cytoskeletal pathology. Proc. Natl. Acad. Sci. U. S. A. 83:4913-17.

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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
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
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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