Title | Calpains as mechanistic drivers and therapeutic targets for ocular disease. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Vu, Jennifer T., Wang Elena, Wu Jolan, Sun Young Joo, Velez Gabriel, Bassuk Alexander G., Lee Soo Hyeon, and Mahajan Vinit B. |
Journal | Trends Mol Med |
Volume | 28 |
Issue | 8 |
Pagination | 644-661 |
Date Published | 2022 08 |
ISSN | 1471-499X |
Keywords | Calcium, 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. |
DOI | 10.1016/j.molmed.2022.05.007 |
Alternate Journal | Trends Mol Med |
PubMed ID | 35641420 |
PubMed Central ID | PMC9345745 |
Grant List | P30 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 |