[Neuronal cell death by Alzheimer's disease-relevant insults and its rescue].
Neuronal cell death accounts for the clinical manifestations in Alzheimer's disease (AD). To establish the curative therapy of AD, neuroprotection is one of the primary therapeutic targets, and the elucidation of the mechanism of neuronal cell death is mandatory. Detailed characterization of neuronal cell death caused by familial AD (FAD)-linked mutant genes revealed that different cell death pathways are evoked by different types of mutants. Humanin (HN), a newly identified neuroprotective peptide, suppresses neuronal cell death caused by all known FAD mutants and A beta, while it has no effect on neuronal cell death caused by AD-irrelevant insults. The functional target of HN is the antagonism to neuronal death, not the modulation of A beta production, suggesting that HN-based medication can be combined with other remedies targeting A beta. HN is a promising seed for a novel therapy aiming at complete cure of AD through the suppression of neuronal loss.
Niikura
Takako
T
Department of Pharmacology, KEIO University School of Medicine.
Hashimoto
Yuichi
Y
Tajima
Hirohisa
H
Ito
Yuko
Y
Nishimoto
Ikuo
I
D000544:Alzheimer Disease / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D016923:Cell Death / Q000502:physiology; D002470:Cell Survival; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics; D053764:Presenilin-1; D053766:Presenilin-2; D011506:Proteins / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D011506:Proteins; C427211:humanin