A novel calpastatin-based inhibitor improves postischemic neurological recovery

Department of Pathology, Henry Ford Hospital, 1 Ford Place, 5D, Detroit, MI 48202, USA.
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 06/2009; 385(1):94-9. DOI: 10.1016/j.bbrc.2009.04.141
Source: PubMed


Calpastatin, a naturally occurring protein, is the only inhibitor that is specific for calpain. A novel blood-brain barrier (BBB)-permeant calpastatin-based calpain inhibitor, named B27-HYD, was developed and used to assess calpain's contribution to neurological dysfunction after stroke in rats. Postischemic administration of B27-HYD reduced infarct volume and neurological deficits by 35% and 44%, respectively, compared to untreated animals. We also show that the pharmacologic intervention has engaged the intended biologic target. Our data further demonstrates the potential utility of SBDP145, a signature biomarker of acute brain injury, in evaluating possible mechanisms of calpain in the pathogenesis of stroke and as an adjunct in guiding therapeutic decision making.

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    • "It is thus reasonable to conclude that the high calpastatin found in the infected cells is responsible for the protective effects of the mycoplasma against Ab-toxicity. Inhibition of calpain activity by exogenous pharmacological means, including calpastatin-based inhibitors, has been considered for therapy of various diseases, in which calpain is involved (Anagli et al., 2009; Pietsch et al., 2010; Ray et al., 2002). Mycoplasmas provide the first naturally occurring biological system that upregulates the endogenous calpain inhibitor, and thus may be of interest in devising treatments for some disorders, such as neurodegenerative diseases and neural damage produced by trauma. "
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