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Calpain-1 and Calpain-2 in the Brain: What Have We Learned from 45 Years of Research?

Year: 2025
Type: article
Abstract: Although the calcium-dependent proteases, calpains, were discovered more than 60 years ago, we still know very little regarding their functions, mostly because very few studies are addressing questions related to specific members of this relatively large family of cysteine proteases. The "classical calpains", calpain-1 and calpain-2, are ubiquitous and have received more attention because of the special roles they play in the brain. The authors have been studying the properties and functions of these two calpain isoforms in the brain for over 45 years, and this review will focus on what has been learned over this period of time. In particular, we will discuss the numerous studies that have led to the notion that calpain-1 and calpain-2 play opposite functions in the brain on processes ranging from neuronal survival or death, synaptic plasticity, and learning and memory to neurogenesis. Mechanisms underlying these opposite functions are starting to be understood and the findings support the notion that such opposite functions might be a general feature of these two isoforms in any type of cell. This review concludes with a discussion of the potential benefits of selective calpain-2 inhibitors for the treatment of a variety of neurological disorders.
Source: Cells
Language: English
Subfield: Cell Biology
Open Access status: gold
Estimated APC paid: $3,258
OpenAlex ID: W4413411663
FWCI: 5.021
Cites: 187
Cited by: 12
Related to: 10