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Neuroprotective strategies against calpain-mediated neurodegeneration

Authors Yildiz-Unal A, Korulu S, Karabay A

Received 28 November 2014

Accepted for publication 6 January 2015

Published 5 February 2015 Volume 2015:11 Pages 297—310

DOI https://doi.org/10.2147/NDT.S78226

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Roger Pinder


Aysegul Yildiz-Unal,1 Sirin Korulu,2 Arzu Karabay3

1Department of Molecular Biology and Genetics, Faculty of Science, Mugla Sitki Koçman University, Kötekli, Mugla, Turkey; 2Department of Molecular Biology and Genetics, Istanbul Arel University, Istanbul Turkey; 3Department of Molecular Biology and Genetics, Faculty of Science and Letters, Istanbul Technical University, Maslak, Istanbul, Turkey

Abstract: Calpains are calcium-dependent proteolytic enzymes that have deleterious effects on neurons upon their pathological over-activation. According to the results of numerous studies to date, there is no doubt that abnormal calpain activation triggers activation and progression of apoptotic processes in neurodegeneration, leading to neuronal death. Thus, it is very crucial to unravel all the aspects of calpain-mediated neurodegeneration in order to protect neurons through eliminating or at least minimizing its lethal effects. Protecting neurons against calpain-activated apoptosis basically requires developing effective, reliable, and most importantly, therapeutically applicable approaches to succeed. From this aspect, the most significant studies focusing on preventing calpain-mediated neurodegeneration include blocking the N-methyl-d-aspartate (NMDA)-type glutamate receptor activities, which are closely related to calpain activation; directly inhibiting calpain itself via intrinsic or synthetic calpain inhibitors, or inhibiting its downstream processes; and utilizing the neuroprotectant steroid hormone estrogen and its receptors. In this review, the most remarkable neuroprotective strategies for calpain-mediated neurodegeneration are categorized and summarized with respect to their advantages and disadvantages over one another, in terms of their efficiency and applicability as a therapeutic regimen in the treatment of neurodegenerative diseases.

Keywords: calpain, neurodegeneration, neuroprotection, calpain inhibitors, NMDAR, Speedy/RINGO

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