title: Humanin and colivelin: neuronal-death-suppressing peptides for Alzheimer's disease and amyotrophic lateral sclerosis.
abstract: Humanin (HN), a 24-amino-acid neuroprotective peptide, was originally found in the occipital lobe of an autopsied Alzheimer's disease (AD) patient. HN inhibits neuronal death by binding to its specific receptor on the cell membrane and triggering a Jak2/STAT3 prosurvival pathway. The activation of this pathway may represent a therapeutic approach to AD. HN also exhibits neuroprotective activity against toxicity by familial amyotrophic lateral sclerosis (ALS)-related mutant superoxide dismutase (SOD1). Recent investigations established that AGA-(C8R)-HNG17, a 17-amno-acid derivative of HN, is 10(5) times more potent as a neuroprotective than HN; at 10-picomolar and higher concentrations in vitro it completely suppresses neuronal death. Moreover, a 26-amino-acid peptide colivelin (CL), composed of activity-dependent neurotrophic factor (ADNF) C-terminally fused to AGA-(C8R)-HNG17, provides complete neuroprotection at 100-femtomolar or higher concentrations in vitro. A series of experiments using mouse AD and ALS models further established the efficacy of HN derivatives, including CL, against these diseases in vivo. HN and CL can be viewed as drug candidates for neuronal death suppression therapy in AD or ALS.
authors.affiliation: Department of Pharmacology, KEIO University School of Medicine, Shnanomachi, Tokyo, Japan. sakimatu@sc.itc.keio.ac.jp
authors.forename: Masaaki
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Sadakazu
authors.initials: S
authors.lastname: Aiso
authors.forename: Ikuo
authors.initials: I
authors.lastname: Nishimoto
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D008954:Models, Biological
chemical_list: C508523:Colivelin; D047908:Intracellular Signaling Peptides and Proteins; C427211:humanin