| Abstrakt: |
Multiple mechanisms are known to contribute to an increase in the intracellular free Ca2+ level. Uncontrolled upregulation of the intracellular free Ca2+ level has been implicated in the pathogenesis of injuries and diseases of the central nervous system (CNS). An increase in the intracellular free Ca2+ level activates the Ca2+-dependent cysteine protease calpain that can mediate neuronal death. Various studies demonstrated that calpain could degrade key cellular substrates so as to impair structural integrity and normal cellular function, leading to both necrotic and apoptotic neuronal death in many CNS disorders. It is now highly recognized from cell culture and animal model studies that calpain has an important role in the mediation of neuronal death in CNS injuries such as ischemic brain injury, spinal cord injury (SCI), and traumatic brain injury (TBI), and also diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), epileptic seizures, Huntington's disease (HD), Parkinson's disease (PD), and multiple sclerosis (MS). In many of these cases, use of calpain inhibitors provided neuroprotection suggesting that calpain could be a potential target for therapeutic interventions. However, currently available calpain inhibitors lack sufficient drug properties that should be addressed adequately before their clinical applications. Importantly, many investigators are now taking interest in developing clinically suitable calpain inhibitors for functional neuroprotection in CNS injuries and diseases. [ABSTRACT FROM AUTHOR] |
