Neuronal cell death in Alzheimer's disease and a neuroprotective factor, humanin.
Brain atrophy caused by neuronal loss is a prominent pathological feature of Alzheimer's disease (AD). Amyloid beta (Abeta), the major component of senile plaques, is considered to play a central role in neuronal cell death. In addition to removal of the toxic Abeta, direct suppression of neuronal loss is an essential part of AD treatment; however, no such neuroprotective therapies have been developed. Excess amount of Abeta evokes multiple cytotoxic mechanisms, involving increase of the intracellular Ca(2+) level, oxidative stress, and receptor-mediated activation of cell-death cascades. Such diversity in cytotoxic mechanisms induced by Abeta 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 Abeta, so far tested. The anti-AD effect of HN has been further confirmed in vivo using mice with Abeta-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.
Niikura
Takako
T
Department of Pharmacology, KEIO University School of Medicine, 35 Shinanomachi, Tokyo 160-8582, Japan. niikurat@sc.itc.keio.ac.jp
Tajima
Hirohisa
H
Kita
Yoshiko
Y