Calpain-2 as a therapeutic target in repeated concussion-induced neuropathy and behavioral impairment.
Sci Adv
; 6(27)2020 07.
Article
en En
| MEDLINE
| ID: mdl-32937436
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Conmoción Encefálica
/
Calpaína
Límite:
Animals
Idioma:
En
Revista:
Sci Adv
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos