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Calpains as mechanistic drivers and therapeutic targets for ocular disease.

TitleCalpains as mechanistic drivers and therapeutic targets for ocular disease.
Publication TypeJournal Article
Year of Publication2022
AuthorsVu, Jennifer T., Wang Elena, Wu Jolan, Sun Young Joo, Velez Gabriel, Bassuk Alexander G., Lee Soo Hyeon, and Mahajan Vinit B.
JournalTrends Mol Med
Volume28
Issue8
Pagination644-661
Date Published2022 08
ISSN1471-499X
KeywordsCalcium, Calpain, Cell Death, Humans, Retina
Abstract

Ophthalmic neurodegenerative diseases encompass a wide array of molecular pathologies unified by calpain dysregulation. Calpains are calcium-dependent proteases that perpetuate cellular death and inflammation when hyperactivated. Calpain inhibition trials in other organs have faced pharmacological challenges, but the eye offers many advantages for the development and testing of targeted molecular therapeutics, including small molecules, peptides, engineered proteins, drug implants, and gene-based therapies. This review highlights structural mechanisms underlying calpain activation, distinct cellular expression patterns, and in vivo models that link calpain hyperactivity to human retinal and developmental disease. Optimizing therapeutic approaches for calpain-mediated eye diseases can help accelerate clinically feasible strategies for treating calpain dysregulation in other diseased tissues.

DOI10.1016/j.molmed.2022.05.007
Alternate JournalTrends Mol Med
PubMed ID35641420
PubMed Central IDPMC9345745
Grant ListP30 EY026877 / EY / NEI NIH HHS / United States
T32 GM139776 / GM / NIGMS NIH HHS / United States
R01 EY030151 / EY / NEI NIH HHS / United States
R01 EY025225 / EY / NEI NIH HHS / United States
F30 EY027986 / EY / NEI NIH HHS / United States
T32 GM007337 / GM / NIGMS NIH HHS / United States
R01 EY031952 / EY / NEI NIH HHS / United States
R01 EY024665 / EY / NEI NIH HHS / United States