Humanin: after the discovery.
Humanin (HN) is a novel neuroprotective factor that consists of 24 amino acid residues. HN suppresses neuronal cell death caused by Alzheimer's disease (AD)-specific insults, including both amyloid-beta (betaAbeta) peptides and familial AD-causative genes. Cerebrovascular smooth muscle cells are also protected from Abeta toxicity by HN, suggesting that HN affects both neuronal and non-neuronal cells when they are exposed to AD-related cytotoxicity. HN peptide exerts a neuroprotective effect through the cell surface via putative receptor(s). HN activates a cellular signaling cascade that intervenes (at least) in activation of c-Jun N-terminal kinase. The highly selective effect of HN on AD-relevant cell death indicates that HN is promising for AD therapy. Additionally, a recent study showed that intracellularly overexpressed HN suppressed mitochondria-mediated apoptosis by inhibiting Bax activity.
Niikura
Takako
T
Department of Pharmacology, KEIO University School of Medicine, Medical Research Building, Tokyo 160-8582, Japan. niikurat@sc.itc.keio.ac.jp
Chiba
Tomohiro
T
Aiso
Sadakazu
S
Matsuoka
Masaaki
M
Nishimoto
Ikuo
I
D000595:Amino Acid Sequence; D000818:Animals; D016923:Cell Death / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; D011506:Proteins; C427211:humanin