Currently evaluated calpain and caspase inhibitors for neuroprotection in experimental brain ischemia.

Currently evaluated calpain and caspase inhibitors for neuroprotection in experimental brain ischemia. Research Abstract Details 

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Currently evaluated calpain and caspase inhibitors for neuroprotection in experimental brain ischemia. Abstract Text:

Swapan K Ray,

Currently available therapies for brain ischemia, with a few exceptions, provide only symptomatic relief in patients. Recent investigations in experimental models provided an understanding of the cellular and molecular mechanisms that lead to neurodegeneration in ischemic injury, and also indicate targets for prevention and amelioration of the devastating consequences of stroke. An enormous increase in intracellular free Ca(2+) levels following stroke activates Ca(2+)-dependent enzymes, contributing to neuronal death and dysfunction. Additionally, ischemic injury generates highly reactive free radicals and triggers release of cytotoxic cytokines for activation of cysteine proteases. A number of studies already indicated a prominent role for the cysteine proteases of the calpain and caspase families in the pathogenesis of brain ischemia. Proteolytic activities of these proteases degrade various cytoskeletal proteins and membrane proteins, destabilizing the structural integrity and forcing the neurons to delayed death in ischemic penumbra. Some current studies have unequivocally confirmed the neuronal apoptosis in ischemia and showed that administration of calpain and caspase inhibitors alone or in combination can provide functional neuroprotection in various animal models of cerebral ischemia. This article will discuss the molecular structures and activities of calpain and caspase inhibitors and their therapeutic efficacy in experimental brain ischemia. However, further investigations are necessary for improvements in the structural design of calpain and caspase inhibitors for their persistent therapeutic efficacy in animal models of stroke and for clinical trials in the future.

Currently evaluated calpain and caspase inhibitors for neuroprotection in experimental brain ischemia. Publishing Authors By Initials

SK Ray,

For similar chemical actions and uses: pharmacologic actions: physiological effects of drugs: protective agents: neuroprotective agents research abstracts see: chemical actions and uses: pharmacologic actions: physiological effects of drugs: protective agents: neuroprotective agents research

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Currently evaluated calpain and caspase inhibitors for neuroprotection in experimental brain ischemia. Journal Published:

PUBLICATION TYPE: Review

Journal: Current medicinal chemistry

VOLUME: 13

Page Numbers: 3425-40

Journal Abbreviation: Curr. Med. Chem.

ISSN: 0929-8673

DAY: 3

MONTH: 12

YEAR: 2006

Currently evaluated calpain and caspase inhibitors for neuroprotection in experimental brain ischemia. Information

Number of References: 250

LANGUAGE: eng

NlmUniqueID: 9440157

Currently evaluated calpain and caspase inhibitors for neuroprotection in experimental brain ischemia. Keywords Mesh Terms:

KEYWORDS: Neuroprotective Agents

MESH TERMS: therapeutic use

Chemical & Substance for Abstract: Currently evaluated calpain and caspase inhibitors for neuroprotection in experimental brain ischemia. Information

Substance Name: Caspases

Registry Number: EC 3.4.22.-

Grant and Affiliation Information for Currently evaluated calpain and caspase inhibitors for neuroprotection in experimental brain ischemia.

AFFILIATION: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA. raysk@musc.edu

Country: Netherlands

AGENCY: United States NINDS

GRANT: NS-57811

ACRONYM: NS

MEDLINETA: Curr Med Chem

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