Humanin: a potential peptide for neuroprotective therapy against Alzheimer's disease

• SELKOE : Alzheimer's disease: genes, proteins, and therapy. Physiol. Rev. (2001) 81:741-766.
   PubMed Web of Science ®Google Scholar
• REISBERG B, DOODY R, STOFFLER A, SCHMITT F, FERRIS S, MOBIUS HJ: Memantine in moderate-to-severe Alzheimer's disease. N. Engl. J. Med. (2003) 348:1333-1341.
   PubMed Web of Science ®Google Scholar
• MORISHIMA-KAWASHIMA M, IHARA Y: Alzheimer's disease: β-amyloid protein and tau. J. Neurosci. Res. (2002) 70:392-401.
   PubMed Web of Science ®Google Scholar
• SELKOE DJ, SCHENK D: Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. Annu. Rev. Pharmacol. Toxicol. (2003) 43:545-584.
   PubMed Web of Science ®Google Scholar
• BUSCIGLIO J, LORENZO A, YEH J, YANKNER B: β-Amyloid fibrils induce tau phosphorylation and loss of microtubule binding. Neuron (1995) 14:879-888.
   PubMed Web of Science ®Google Scholar
• IWATSUBO T: The γ-secretase complex: machinery for intramembrane proteolysis. Curr. Opin. Neurobiol. (2004) 14:379-383.
   PubMed Web of Science ®Google Scholar
• WALSH DM, SELKOE DJ: Deciphering the molecular basis of memory failure in Alzheimer's disease. Neuron (2004) 30:181-193.
   Google Scholar
• TABIRA T, CHUI DH, KURODA S: Significance of intracellular Aβ42 accumulation in Alzheimer's disease. Front. Biosci. (2002) 7:A44-A49.
   PubMed Web of Science ®Google Scholar
• KIENLEN-CAMPARD P, MIOLET S, TASIAUX B, OCTAVE JN: Intracellular amyloid-β1-42, but not extracellular soluble amyloid-β peptides, induces neuronal apoptosis. J. Biol. Chem. (2002) 277:15666-15670.
   PubMed Web of Science ®Google Scholar
• AISEN PS: The development of anti-amyloid therapy for Alzheimer's disease. CNS Drug (2005) 19:989-996.
   PubMed Web of Science ®Google Scholar
• NIIKURA T, HASHIMOTO Y, TAJIMA H, NISHIMOTO I: Death and survival of neuronal cells exposed to Alzheimer's insults. J. Neurosci. Res. (2002) 70:380-391.
   PubMed Web of Science ®Google Scholar
• SELKOE DJ: Alzheimer's disease is a synaptic failure. Science (2002) 298:789-791.
   PubMed Web of Science ®Google Scholar
• YAMATSUJI T, OKAMOTO T, TAKEDA S et al.: G-protein-mediated neuronal DNA fragmentation by familial Alzheimer's disease-associated V642 mutants of APP. Science (1996) 272:1349-1352.
   PubMed Web of Science ®Google Scholar
• NIIKURA T, MURAYAMA N, HASHIMOTO Y et al.: V642I APP-inducible neuronal cells: a model system for investigating Alzheimer's disorders. Biochem. Biophys. Res. Commun. (2000) 274:445-454.
   PubMed Web of Science ®Google Scholar
• NIIKURA T, YAMADA M, CHIBA T, AISO S, MATSUOKA M, NISHIMOTO I: Characterization of V642I-AβPP-induced cytotoxicity in primary neurons. J. Neurosci. Res. (2004) 77:54-62.
   PubMed Web of Science ®Google Scholar
• HASHIMOTO Y, NIIKURA T, ITO Y, NISHIMOTO I: Multiple mechanisms underlie neurotoxicity by different types of Alzheimer's disease mutations of amyloid precursor protein. J. Biol. Chem. (2000) 275:34541-34551.
   PubMed Web of Science ®Google Scholar
• YAMATSUJI T, OKAMOTO T, TAKEDA S, MURAYAMA Y, YANAKA N, NISHIMOTO I: Expression of V642 APP mutant causes cellular apoptosis as Alzheimer trait-linked phenotype. EMBO J. (1996) 15:498-509.
   PubMed Web of Science ®Google Scholar
• NIIKURA T, HASHIMOTO Y, OKAMOTO T et al.: Insulin-like growth factor I (IGF-I) protects cells from apoptosis by Alzheimer's V642I mutant APP through IGF-I receptor in an IGF-binding protein-sensitive manner. J. Neurosci. (2001) 21:1902-1910.
   PubMed Web of Science ®Google Scholar
• HASHIMOTO Y, ITO Y, ARAKAWA E et al.: Neurotoxic mechanisms triggered by Alzheimer's disease-linked mutant M146L presenilin 1: involvement of NO synthase via a novel pertussis toxin target. J. Neurochem. (2002) 80:426-437.
   PubMed Web of Science ®Google Scholar
• HASHIMOTO Y, NIIKURA T, ITO Y, KITA Y, TERASHITA K, NISHIMOTO I: Neurotoxic mechanisms by Alzheimer's disease-linked N141I mutant of presenilin 2. J. Pharmacol. Exp. Ther. (2002) 300:736-745.
   PubMed Web of Science ®Google Scholar
• HASHIMOTO Y, TSUKAMOTO E, NIIKURA T et al.: Amino- and carboxyl-terminal mutants of presenilin 1 cause neuronal cell death through distinct toxic mechanisms: study of 27 different presenilin 1 mutants. J. Neurosci. Res. (2004) 75:417-428.
   PubMed Web of Science ®Google Scholar
• ABE Y, HASHIMOTO Y, TOMITA Y et al.: Cytotoxic mechanisms by M239V presenilin 2, a little-analyzed Alzheimer's disease-causative mutant. J. Neurosci. Res. (2004) 77:583-595.
   PubMed Web of Science ®Google Scholar
• WOLOZIN B, IWASAKI K, VITO P et al.: Participation of presenilin 2 in apoptosis: enhanced basal activity conferred by an Alzheimer mutation. Science (1996) 274:1710-1713.
   PubMed Web of Science ®Google Scholar
• WOLOZIN B, ALEXANDER P, PALACINO J: Regulation of apoptosis by presenilin 1. Neurobiol. Aging (1998) 19:S23-S27.
   PubMed Web of Science ®Google Scholar
• ARAKI W, YUASA K, TAKEDA S, SHIROTANI K, TAKAHASHI K, TABIRA T: Overexpression of presenilin-2 enhances apoptotic death of cultured cortical neurons. Ann. NY Acad. Sci. (2000) 920:241-244.
   PubMed Web of Science ®Google Scholar
• CHUI DH, TANAHASHI H, OZAWA K et al.: Transgenic mice with Alzheimer presenilin 1 mutations show accelerated neurodegeneration without amyloid plaque formation. Nat. Med. (1999) 5:560-564.
   PubMed Web of Science ®Google Scholar
• GUO Q, FU W, HOLTSBERG FW, STEINER SM, MATTSON MP: Superoxide mediates the cell-death-enhancing action of presenilin-1 mutations. J. Neurosci. Res. (1999) 56:457-470.
   PubMed Web of Science ®Google Scholar
• WEIHL CC, GHADGE GD, KENNEDY GS, HAY N, MILLER RJ, ROO RP: Mutant presenilin-1 induces apoptosis and downregulates Akt/PKB. J. Neurosci. (1999) 19:5360-5369.
   PubMed Web of Science ®Google Scholar
• NIIKURA T, NISHIMOTO I: Neuronal cell death in Alzheimer's disease and its potential therapy with neuroprotective factors. In: Frontiers in Alzheimer's Disease Research. Welsh EM (Ed.), Nova Science Publishers, New York (2006):55-96.
   Google Scholar
• VITO P, LACANA E, D'ADAMIO L: Interfering with apoptosis: Ca(2+)-binding protein ALG-2 and Alzheimer's disease gene ALG-3. Science (1996) 271:521-525.
   PubMed Web of Science ®Google Scholar
• D'ADAMIO L, LACANA E, VITO P: Functional cloning of genes involved in T-cell receptor-induced programmed cell death. Semin. Immunol. (1997) 9:17-23.
   PubMedGoogle Scholar
• VITO P, WOLOZIN B, GANJEI JK, IWASAKI K, LACANA E, D'ADAMIO L: Requirement of the familial Alzheimer's disease gene PS2 for apoptosis. J. Biol. Chem. (1996) 271:31025-31028.
   PubMed Web of Science ®Google Scholar
• ARAKI W, YUASA K, TAJEDA S, SHIROTANI K, TAKAHASHI K, TABIRA T: Overexpression of presenilin-2 enhances apoptotic death of cultured cortical neurons. Ann. NY Acad. Sci. (2000) 920:241-244.
   PubMed Web of Science ®Google Scholar
• ALVES DA COSTA C, MATTSON MP, ANCOLIO K, CHECLER F: The C-terminal fragment of presenilin 2 triggers p53-mediated staurosporine-induced apoptosis, a function independent of the presenilinase-derived N-terminal counterpart. J. Biol. Chem. (2003) 278:12064-12069.
   PubMed Web of Science ®Google Scholar
• QIN W, PENG Y, KSIEZAK-REDING H et al.: Inhibition of cyclooxygenase as potential novel therapeutic strategy in N141I presenilin-2 familial Alzheimer's disease. Mol. Psychiatry (2006) 11:172-181.
   PubMed Web of Science ®Google Scholar
• HASHIMOTO Y, NIIKURA T, TAJIMA H et al.: A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Aβ. Proc. Natl. Acad. Sci. USA (2001) 98:6336-6341.
   PubMed Web of Science ®Google Scholar
• HASHIMOTO Y, TSUJI O, KANEKURA K et al.: The Gtx homeodomain transcription factor exerts neuroprotection using its homeodomain. J. Biol. Chem. (2004) 279:16767-16777.
   PubMed Web of Science ®Google Scholar
• YAMAGISHI Y, HASHIMOTO Y, NIIKURA T, NISHIMOTO I: Identification of essential amino acids in Humanin, a neuroprotective factor against Alzheimer's disease relevant insults. Peptides (2003) 24:585-595.
   PubMed Web of Science ®Google Scholar
• HASHIMOTO Y, ITO Y, NIIKURA T et al.: Mechanisms of neuroprotection by a novel rescue factor Humanin from Swedish mutant amyloid precursor protein. Biochem. Biophys. Res. Commun. (2001) 283:460-468.
   PubMed Web of Science ®Google Scholar
• HASHIMOTO Y, NIIKURA T, ITO Y et al.: Detailed characterization of neuroprotection by a rescue factor humanin against various Alzheimer's disease-relevant insults. J. Neurosci. (2001) 21:9235-9245.
   PubMed Web of Science ®Google Scholar
• TERASHITA K, HASHIMOTO Y, NIIKURA T et al.: Two serine residues distinctly regulate the rescue function of Humanin, an inhibiting factor of Alzheimer's disease-related neurotoxicity: functional potentiation by isomerization and dimerization. J. Neurochem. (2003) 85:1521-1538.
   PubMed Web of Science ®Google Scholar
• MANNING M, BALASPIRI L, MOEHRING J: Synthesis and some pharmacological properties of deamino [4-threonine,8-D-arginine] vasopressin and deamino [8-D-arginine] vasopressin, highly potent and specific antidiuretic peptides, and [8-D-arginie] vasopressin and deamino-arginine-vasopressin. J. Med. Chem. (1976) 19:842-845.
   PubMed Web of Science ®Google Scholar
• ROHER AE, LOWENSON JD, CLARKE S et al.: Structural alternations in the peptide backbone of β-amyloid core protein may account for its deposition and stability in Alzheimer's disease. J. Biol. Chem. (1993) 268:3072-3038.
   PubMed Web of Science ®Google Scholar
• WOLOSKER H, BLACKSHAW S, SNYDER SH: Serine racemase: a glial enzyme synthesizing D-serine to regulate glutamate-N-methyl-D-aspartate neurotransmission. Proc. Natl. Acad. Sci. USA (1999) 96:13409-13414.
   PubMed Web of Science ®Google Scholar
• BENAKI D, ZIKOS C, EVANGELOU A et al.: Solution structure of humanin, a peptide against Alzheimer's disease-related neurotoxicity. Biochem. Biophys. Res. Commun. (2005) 329:152-160.
   PubMed Web of Science ®Google Scholar
• BENAKI D, ZIKOS C, EVANGELOU A et al.: Solution structure of Ser14Gly-humanin, a potent rescue factor against neuronal cell death in Alzheimer's disease. Biochem. Biophys. Res. Commun. (2006) 349:634-642.
   PubMed Web of Science ®Google Scholar
• ARAKAWA T, NIIKURA T, TAJIMA H, KITA Y: The secondary structure analysis of a potent Ser14Gly analog of antiAlzheimer peptide, Humanin, by circular dichroism. J. Pept. Sci. (2006) 12:639-642.
   PubMed Web of Science ®Google Scholar
• HASHIMOTO Y, SUZUKI H, AISO S, NIIKURA T, NISHIMOTO I, MATSUOKA M: Involvement of tyrosine kinases and STAT3 in Humanin-mediated neuroprotection. Life Sci. (2005) 77:3092-3104.
   PubMed Web of Science ®Google Scholar
• LE Y, GONG Y, LI B et al.: Utilization of two seven-transmembrane, G protein-coupled receptors, formyl peptide receptor-like 1 and formyl peptide receptor, by the synthetic hexapeptide WKYMVm for human phagocyte activation. J. Immunol. (1999) 163:6777-6784.
   PubMed Web of Science ®Google Scholar
• HARADA M, HABATA Y, HOSOYA M et al.: N-Formylated humanin activates both formyl peptide receptor-like 1 and 2. Biochem. Biophys. Res. Commun. (2004) 324:255-261.
   PubMed Web of Science ®Google Scholar
• HOLSTER-COCHAV M, DIVINSKI I, GOZES I: Tubulin is the target binding site for NAP-related peptides: ADNF-9, D-NAP, and D-SAL. J. Mol. Neurosci. (2006) 28:303-307.
   PubMed Web of Science ®Google Scholar
• TAJIMA H, KAWASUMI M, CHIBA T et al.: A humanin derivative, S14G-HN, prevents amyloid-β-induced memory impairment in mice. J. Neurosci. Res. (2005) 79:714-723.
   PubMed Web of Science ®Google Scholar
• MAMIYA T, UKAI M: [Gly(14)]-Humanin improved the learning and memory impairment induced by scopolamine in vivo. Br. J. Pharmacol. (2001) 134:1597-1599.
   PubMed Web of Science ®Google Scholar
• KREJCOVA G, PATOCKA J, SLANINOVA J: Effect of humanin analogues on experimentally induced impairment of spatial memory in rats. J. Pept. Sci. (2004) 10:636-639.
   PubMed Web of Science ®Google Scholar
• IKONEN M, LIU B, HASHIMOTO Y et al.: Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis. Proc. Natl. Acad. Sci. USA (2003) 100:13042-13047.
   PubMed Web of Science ®Google Scholar
• LEE KW, LIU B, MA L et al.: Cellular internalization of insulin-like growth factor binding protein-3: distinct endocytic pathways facilitate reuptake and nuclear localization. J. Biol. Chem. (2004) 279:469-476.
   PubMed Web of Science ®Google Scholar
• KARIYA S, TAKAHASHI N, OOBA N, KAWAHARA M, NAKAYAMA H, UENO S: Humanin inhibits cell death of serum-deprived PC12h cells. Neuroreport (2002) 13:903-907.
   PubMed Web of Science ®Google Scholar
• JUNG SS, VAN NOSTRAND WE: Humanin rescues human cerebrovascular smooth muscle cells from Aβ-induced toxicity. J. Neurochem. (2003) 84:266-272.
   PubMed Web of Science ®Google Scholar
• COLON E, STRAND ML, CARLSSON-SKWIRUT C et al.: Anti-apoptotic factor humanin is expressed in the testis and prevents cell-death in leydig cells during the first wave of spermatogenesis. J. Cell. Physiol. (2006) 208:373-385.
   PubMed Web of Science ®Google Scholar
• WANG D, LI H, YUAN H et al.: Humanin delays apoptosis in K562 cells by downregulation of P38 MAP kinase. Apoptosis (2005) 10:963-971.
   PubMed Web of Science ®Google Scholar
• GUO B, ZHAI D, CABEZAS E et al.: Humanin peptide suppresses apoptosis by interfering with Bax activation. Nature (2003) 423:456-461.
   PubMed Web of Science ®Google Scholar
• SPONNE I, FIFRE A, KOZIEL V, KRIEM B, OSTER T, PILLOT T: Humanin rescues cortical neurons from prion-peptide-induced apoptosis. Mol. Cell. Neurosci. (2004) 25:95-102.
   PubMed Web of Science ®Google Scholar

Patent

• KEIO UNIVERSITY: WO01/21787, EP1221480 (2002).
   Google Scholar