| First Author | Wang Y | Year | 2020 |
| Journal | Sci Adv | Volume | 6 |
| Issue | 27 | PubMed ID | 32937436 |
| Mgi Jnum | J:317132 | Mgi Id | MGI:6796277 |
| Doi | 10.1126/sciadv.aba5547 | Citation | Wang Y, et al. (2020) Calpain-2 as a therapeutic target in repeated concussion-induced neuropathy and behavioral impairment. Sci Adv 6(27) |
| abstractText | Repeated concussion represents a serious health problem as it can result in various brain pathologies, ranging from minor focal tissue injury to severe chronic traumatic encephalopathy. The calcium-dependent protease, calpain, participates in the development of neurodegeneration following concussion, but there is no information regarding the relative contribution of calpain-1 and calpain-2, the major calpain isoforms in the brain. We used a mouse model of repeated concussions, which reproduces most of the behavioral and neuropathological features of the human condition, to address this issue. Deletion of calpain-2 or treatment with a selective calpain-2 inhibitor for 2 weeks prevented most of these neuropathological features. Changes in TAR DNA binding protein 43 (TDP-43) subcellular localization similar to those found in human amyotrophic lateral sclerosis and frontotemporal dementia were also prevented by deletion of calpain-2 or treatment with calpain-2 inhibitor. Our results indicate that a selective calpain-2 inhibitor represents a therapeutic approach for concussion. |
