Brain atrophy caused by neuronal loss is a prominent pathological feature of Alzheimers disease (AD). Amyloid (A ), the major component of senile plaques, is considered to play a central role in neuronal cell death. In addition to removal of the toxic Aβ , direct suppression of neuronal loss is an essential part of AD treatment; however, no such neuroprotective therapies have been developed. Excess amount of Aβ evokes multiple cytotoxic mechanisms, involving increase of the intracellular Ca2+ level, oxidative stress, and receptor-mediated activation of cell-death cascades. Such diversity in cytotoxic mechanisms induced by Aβ clearly indicates a complex nature of the AD-related neuronal cell death. We have identified a 24-residue peptide, Humanin (HN), which suppresses in vitro neuronal cell death caused by all AD-related insults, including Aβ , so far tested. The anti-AD effect of HN has been further confirmed in vivo using mice with Aβ -induced amnesia. Altogether, such potent neuroprotective activity of HN against AD-relevant cytotoxicity both in vitro and in vivo suggests the potential clinical applications of HN in novel AD therapies aimed at controlling neuronal death.
Keywords: Alzheimer's disease, neuronal death, amyloid, amyloid precursor protein (APP), presenilin (PS), Humanin (HN), neuroprotection
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