Calpastatin Overexpression Protects against Excitotoxic Hippocampal Injury and Traumatic Spinal Cord Injury.
calpastatin overexpression
hippocampal injury
spinal cord injury
Journal
Journal of neurotrauma
ISSN: 1557-9042
Titre abrégé: J Neurotrauma
Pays: United States
ID NLM: 8811626
Informations de publication
Date de publication:
01 11 2020
01 11 2020
Historique:
pubmed:
29
7
2020
medline:
6
11
2021
entrez:
29
7
2020
Statut:
ppublish
Résumé
Small molecule inhibitors of calcium-dependent proteases, calpains (CAPNs), protect against neurodegeneration induced by a variety of insults including excitotoxicity and spinal cord injury (SCI). Many of these compounds, however, also inhibit other proteases, which has made it difficult to evaluate the contribution of calpains to neurodegeneration. Calpastatin is a highly specific endogenous inhibitor of classical calpains, including CAPN1 and CAPN2. In the present study, we utilized transgenic mice that overexpress human calpastatin under the prion promoter (PrP-hCAST) to evaluate the hypothesis that calpastatin overexpression protects against excitotoxic hippocampal injury and contusive SCI. The PrP-hCAST organotypic hippocampal slice cultures showed reduced neuronal death and reduced calpain-dependent proteolysis (α-spectrin breakdown production, 145 kDa) at 24 h after N-methyl-D-aspartate (NMDA) injury compared with the wild-type (WT) cultures (
Identifiants
pubmed: 32718209
doi: 10.1089/neu.2020.7122
pmc: PMC7585603
doi:
Substances chimiques
CAST protein, human
0
Calcium-Binding Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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