Skip to main content

Advertisement

SpringerLink
Log in

Humanin and the Receptors for Humanin

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Alzheimer’s disease (AD) is a prevalent dementia-causing neurodegenerative disease. Neuronal death is closely linked to the progression of AD-associated dementia. Accumulating evidence has established that a 24-amino-acid bioactive peptide, Humanin, protects neurons from AD-related neuronal death. A series of studies using various murine AD models including familial AD gene-expressing transgenic mice have shown that Humanin is effective against AD-related neuronal dysfunction in vivo. Most recently, it has been shown that Humanin inhibits neuronal cell death and dysfunction by binding to a novel IL-6-receptor-related receptor(s) on the cell surface involving CNTFRα, WSX-1, and gp130. These findings suggest that endogenous Humanin [or a Humanin-like substance(s)] may suppress the onset of AD-related dementia by inhibiting both AD-related neuronal cell death and dysfunction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Marx J (2007) Alzheimer’s disease. Fresh evidence points to an old suspect: calcium. Science 318:384

    Article  PubMed  CAS  Google Scholar 

  2. Matsuoka M (2009) Humanin: a defender against Alzheimer’s disease? Recent Pat CNS Drug Discov 4:37–42

    Article  PubMed  CAS  Google Scholar 

  3. Hashimoto Y, Niikura T, Tajima H, YasukawaT SH, Ito Y, Kita Y, Kawasumi M, Kouyama K, Doyu M, Sobue G, Koide T, Tsuji S, Lang J, Kurokawa K, Nishimoto I (2001) A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer’s disease genes and Aβ. Proc Natl Acad Sci USA 98:6336–6341

    Article  PubMed  CAS  Google Scholar 

  4. Nishimoto I, Matsuoka M, Niikura T (2004) Unravelling the role of Humanin. Trends Mol Med 10:102–105

    Article  PubMed  CAS  Google Scholar 

  5. Matsuoka M, Hashimoto Y, Aiso S, Nishimoto I (2006) Humanin and colivelin: neuronal-death-suppressing peptides for Alzheimer’s disease and amyotrophic lateral sclerosis. CNS Drug Rev 12:113–122

    Article  PubMed  CAS  Google Scholar 

  6. Hashimoto Y, Kurita M, Aiso S, Nishimoto I, Matsuoka M (2009) Humanin inhibits neuronal cell death by interacting with a cytokine receptor complex or complexes involving CNTF receptor α/WSX-1/gp130. Mol Biol Cell 20:2864–2873

    Article  PubMed  CAS  Google Scholar 

  7. Selkoe DJ (1991) The molecular pathology of Alzheimer’s disease. Neuron 6:487–498

    Article  PubMed  CAS  Google Scholar 

  8. Hardy J, Allsop D (1991) Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol Sci 12:383–388

    Article  PubMed  CAS  Google Scholar 

  9. Hardy JA, Higgins GA (1992) Alzheimer’s disease, the amyloid cascade hypothesis. Science 286:184–185

    Article  Google Scholar 

  10. Hardy JA, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297:353–356

    Article  PubMed  CAS  Google Scholar 

  11. Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat Rev Mol Cell Biol 8:101–112

    Article  PubMed  CAS  Google Scholar 

  12. Walsh DM, Selkoe DJ (2007) A beta oligomers—a decade of discovery. J Neurochem 101:1172–1184

    Article  PubMed  CAS  Google Scholar 

  13. Selkoe DJ (2008) Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior. Behav Brain Res 192:106–113

    Article  PubMed  CAS  Google Scholar 

  14. Hardy J (2009) The amyloid hypothesis for Alzheimer’s disease: a critical reappraisal. J Neurochem 110:1129–1134

    Article  PubMed  CAS  Google Scholar 

  15. Sherrington R, Rogaev EI, Liang Y, Rogaeva E, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K, Tsuda T, Mar L, Foncin J, Bruni A, Montesi M, Sorbi S, Rainero I, Pinessi L, Nee L, Chumakov I, Pollen D, Brookes A, Sanseau P, Polinsky R, Wasco W, Da Silva H, Haines J, Pericak-Vance M, Tanzi R, Roses A, Fraser P, Rommens J, St George-Hyslop P (1995) Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease. Nature 375:754–760

    Article  PubMed  CAS  Google Scholar 

  16. Rogaev EI, Sherrington R, Rogaeva EA, Levesque G, Ikeda M, Liang Y, Chi H, Lin C, Holman K, Tsuda T, Mar L, Sorbi S, Nacmias B, Piacentini S, Amaducci L, Chumakov I, Cohen D, Lannfelt L, Fraser P, Rommens J, St George-Hyslop P (1995) Familial Alzheimer’s disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer’s disease type 3 gene. Nature 376:775–778

    Article  PubMed  CAS  Google Scholar 

  17. Levy-Lahad E, Wasco W, Poorkaj P, Romano D, Oshima J, Pettingell W, Yu C, Jondro P, Schmidt S, Wang K (1995) Candidate gene for the chromosome 1 familial Alzheimer’s disease locus. Science 269:973–977

    Article  PubMed  CAS  Google Scholar 

  18. Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N, Bird T, Hardy J, Hutton M, Kukull W, Larson E, Levy-Lahad E, Viitanen M, Peskind E, Poorkaj P, Schellenberg G, Tanzi R, Wasco W, Lannfelt L, Selkoe D, Younkin S (1996) Secreted amyloid β-protein similar to that in the senile plaques of Alzheimer’s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer’s disease. Nature Med 2:864–869

    Article  PubMed  CAS  Google Scholar 

  19. Borchelt DR, Thinakaran G, Eckman CB, Lee M, Davenport F, Ratovitsky T, Prada C, Kim G, Seekins S, Yager D, Slunt H, Wang R, Seeger M, Levey A, Gandy S, Copeland N, Jenkins N, Price D, Younkin S, Sisodia S (1996) Familial Alzheimer’s disease-linked presenilin 1 variants elevate Abeta1–42/1–40 ratio in vitro and in vivo. Neuron 17:1005–1013

    Article  PubMed  CAS  Google Scholar 

  20. Duff K, Eckman C, Zehr C, Yu X, Prada C, Perez-tur J, Hutton M, Buee L, Harigaya Y, Yager D, Morgan D, Gordon M, Holcomb L, Refolo L, Zenk B, Hardy J, Younkin S (1996) Increased amyloid-β 42(43) in brains of mice expressing mutant presenilin 1. Nature 383:710–713

    Article  PubMed  CAS  Google Scholar 

  21. De Strooper B, Saftig P, Craessaerts K, Vanderstichele H, Guhde G, Annaert W, Von Figura K, Van Leuven F (1998) Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391:387–390

    Article  PubMed  CAS  Google Scholar 

  22. Wolfe MS, Xia W, Ostaszewski BL, Diehl TS, Kimberly WT, Selkoe DJ (1999) Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. Nature 398:513–517

    Article  PubMed  CAS  Google Scholar 

  23. Selkoe DJ (2002) Alzheimer’s disease is a synaptic failure. Science 25:789–791

    Article  CAS  Google Scholar 

  24. Morrissette DA, Parachikova A, Green KN, LaFerla FM (2009) Relevance of transgenic mouse models to human Alzheimer disease. J Biol Chem 284:6033–6037

    Article  PubMed  CAS  Google Scholar 

  25. Kokjohn TA, Roher AE (2009) Amyloid precursor protein transgenic mouse models and Alzheimer’s disease: understanding the paradigms, limitations, and contributions. Alzheimers Dement 5:340–347

    Article  PubMed  CAS  Google Scholar 

  26. Killiany RJ, Gomez-Isla T, Moss M, Kikinis R, Sandor T, Jolesz F, Tanzi R, Jones K, Hyman B, Albert M (2000) Use of structural magnetic resonance imaging to predict who will get Alzheimer’s disease. Ann Neurol 47:430–439

    Article  PubMed  CAS  Google Scholar 

  27. Pennanen C, Kivipelto M, Tuomainen S, Hartikainen P, Hänninen T, Laakso M, Hallikainen M, Vanhanen M, Nissinen A, Helkala E, Vainio P, Vanninen R, Partanen K, Soininen H (2004) Hippocampus and entorhinal cortex in mild cognitive impairment and early AD. Neurobiol Aging 25:303–310

    Article  PubMed  Google Scholar 

  28. Becker JT, Davis SW, Hayashi KM, Becker J, Davis S, Hayashi K, Meltzer C, Toga A, Lopez O, Thompson P (2006) Three-dimensional patterns of hippocampal atrophy in mild cognitive impairment. Arch Neurol 63:97–101

    Article  PubMed  Google Scholar 

  29. DeCarli C, Frisoni GB, Clark CM, Harvey D, Grundman M, Petersen R, Thal L, Jin S, Jack C, Scheltens P (2007) Qualitative estimates of medial temporal atrophy as a predictor of progression from mild cognitive impairment to dementia. Arch Neurol 64:108–115

    Article  PubMed  Google Scholar 

  30. McEvoy LK, Fennema-Notestine C, Roddey JC, Hagler DJ Jr, Holland D, Karow DS, Pung CJ, Brewer JB, Dale AM (2009) For the Alzheimer’s disease neuroimaging initiative Alzheimer disease: quantitative structural neuroimaging for detection and prediction of clinical and structural changes in mild cognitive impairment. Radiology 251:195–205

    Article  PubMed  Google Scholar 

  31. Duara R, Loewenstein DA, Potter E, Appel J, Greig MT, Urs R, Shen Q, Raj A, Small B, Barker W, Schofield E, Wu Y, Potter H (2008) Medial temporal lobe atrophy on MRI scans and the diagnosis of Alzheimer disease. Neurology 71:1986–1992

    Article  PubMed  CAS  Google Scholar 

  32. Urs R, Potter E, Barker W, Appel J, Loewenstein DA, Zhao W, Duara R (2009) Visual rating system for assessing magnetic resonance images: a tool in the diagnosis of mild cognitive impairment and Alzheimer disease. J Comput Assist Tomogr 33:73–78

    Article  PubMed  Google Scholar 

  33. Leow AD, Yanovsky I, Parikshak N, Hua X, Lee S, Toga AW, Jack CR Jr, Bernstein MA, Britson PJ, Gunter JL, Ward CP, Borowski B, Shaw LM, Trojanowski JQ, Fleisher AS, Harvey D, Kornak J, Schuff N, Alexander GE, Weiner MW, Thompson PM (2009) The Alzheimer’s disease neuroimaging initiative Alzheimer’s disease neuroimaging initiative: a one-year follow up study using tensor-based morphometry correlating degenerative rates biomarkers and cognition. Neuroimage 45:645–655

    Article  PubMed  Google Scholar 

  34. Henneman WJ, Sluimer JD, Barnes J, van der Flier WM, Sluimer IC, Fox NC, Scheltens P, Vrenken H, Barkhof F (2009) Hippocampal atrophy rates in Alzheimer disease: added value over whole brain volume measures. Neurology 72:999–1007

    Article  PubMed  CAS  Google Scholar 

  35. Jack CR Jr, Lowe VJ, Weigand SD, Wiste HJ, Senjem ML, Knopman DS, Shiung MM, Gunter JL, Boeve BF, Kemp BJ, Weiner M, Petersen RC (2009) Alzheimer’s disease neuroimaging initiative. Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer’s disease: implications for sequence of pathological events in Alzheimer’s disease. Brain 132:1355–1365

    Article  PubMed  Google Scholar 

  36. Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, Bayer A, Jones R, Bullock R, Love S, Neal J, Zotova E, Nicoll J (2008) Long-term effects of Abeta42 immunisation in Alzheimer’s disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet 372:216–223

    Article  PubMed  CAS  Google Scholar 

  37. Savva GM, Wharton SB, Ince PG, Forster G, Matthews FE, Brayne C (2009) Medical research council cognitive function and ageing study. Age, neuropathology, and dementia. N Engl J Med 360:2302–2309

    Article  PubMed  CAS  Google Scholar 

  38. Davis DG, Schmitt FA, Wekstein DR, Markesbery WR (1999) Alzheimer neuropathologic alterations in aged cognitively normal subjects. J Neuropathol Exp Neurol 58:376–388

    Article  PubMed  CAS  Google Scholar 

  39. Bennett DA, Schneider JA, Arvanitakis Z, Kelly J, Aggarwal N, Shah R, Wilson R (2006) Neuropathology of older persons without cognitive impairment from two community-based studies. Neurology 66:1837–1844

    Article  PubMed  CAS  Google Scholar 

  40. Haroutunian V, Schnaider-Beeri M, Schmeidler J, Wysocki M, Purohit D, Perl D, Libow L, Lesser G, Maroukian M, Grossman H (2008) Role of the neuropathology of Alzheimer disease in dementia in the oldest-old. Arch Neurol 65:1211–1217

    Article  PubMed  Google Scholar 

  41. Silver MH, Newell K, Brady C, Hedley-White E, Perls TT (2002) Distinguishing between neurodegenerative disease and disease-free aging: correlating neuropsychological evaluations and neuropathological studies in centenarians. Psychosom Med 64:493–501

    PubMed  Google Scholar 

  42. Ewbank DC, Arnold SE (2009) Cool with plaques and tangles. N Engl J Med 360:2357–2359

    Article  PubMed  CAS  Google Scholar 

  43. Mamiya T, Ukai M (2001) [Gly(14)]-Humanin improved the learning and memory impairment induced by scopolamine in vivo. Br J Pharmacol 134:1597–1599

    Article  PubMed  CAS  Google Scholar 

  44. Krejcova G, Patocka J, Slaninova J (2004) Effect of humanin analogues on experimentally induced impairment of spatial memory in rats. J Pept Sci 10:636–639

    Article  PubMed  CAS  Google Scholar 

  45. Chiba T, Yamada M, Hashimoto Y, Sato M, Sasabe J, Kita Y, Terashita K, Aiso S, Nishimoto I, Matsuoka M (2005) Development of a femtomolar-acting humanin derivative named colivelin by attaching activity-dependent neurotrophic factor to its N terminus: characterization of colivelin-mediated neuroprotection against Alzheimer’s disease-relevant insults in vitro and in vivo. J Neurosci 25:10252–10261

    Article  PubMed  CAS  Google Scholar 

  46. Tajima H, Kawasumi M, Chiba T, Yamada M, Yamashita K, Nawa M, Kita Y, Kouyama K, Aiso S, Matsuoka M, Niikura T, Nishimoto I (2005) A humanin derivative, S14G-HN, prevents amyloid-beta-induced memory impairment in mice. J Neurosci Res 79:714–723

    Article  PubMed  CAS  Google Scholar 

  47. Yamada M, Chiba T, Sasabe J, Terashita K, Aiso S, Matsuoka M (2008) Nasal colivelin treatment ameliorates memory impairment related to Alzheimer’s disease. Neuropsychopharmaco 33:2020–2032

    Article  CAS  Google Scholar 

  48. Miao J, Zhang W, Yin R, Liu R, Su C, Lei G, Li Z (2008) S14G-Humanin ameliorates Abeta25–35-induced behavioral deficits by reducing neuroinflammatory responses and apoptosis in mice. Neuropeptides 42:557–567

    Article  PubMed  CAS  Google Scholar 

  49. Kunesová G, Hlavácek J, Patocka J, Evangelou A, Zikos C, Benaki D, Paravatou-Petsotas M, Pelecanou M, Livaniou E, Slaninova J (2008) The multiple T-maze in vivo testing of the neuroprotective effect of humanin analogues. Peptides 29:1982–1987

    Article  PubMed  CAS  Google Scholar 

  50. Chiba T, Yamada M, Sasabe J, Terashita K, Shimoda M, Matsuoka M, Aiso S (2009) Amyloid-beta causes memory impairment by disturbing the JAK2/STAT3 axis in hippocampal neurons. Mol Psychiatry 14:206–222

    Article  PubMed  CAS  Google Scholar 

  51. Chiba T, Hashimoto Y, Tajima H, Yamada M, Kato R, Niikura T et al (2004) Neuroprotective effect of activity-dependent neurotrophic factor against toxicity from familial amyotrophic lateral sclerosis-linked mutant SOD1 in vitro and in vivo. J Neurosci Res 78:542–552

    Article  PubMed  CAS  Google Scholar 

  52. Kariya S, Takahashi N, Ooba N, Kawahara M, Nakayama H, Ueno S (2002) Humanin inhibits cell death of serum-deprived PC12h cells. NeuroReport 13:903–907

    Article  PubMed  CAS  Google Scholar 

  53. Kariya S, Hirano M, Nagai Y, Furiya Y, Fujikake N, Toda T et al (2005) Humanin attenuates apoptosis induced by DRPLA proteins with expanded polyglutamine stretches. J Mol Neurosci 25:165–169

    Article  PubMed  CAS  Google Scholar 

  54. Xu X, Chua CC, Gao J, Hamdy RC, Chua BH (2006) Humanin is a novel neuroprotective agent against stroke. Stroke 37:2613–2619

    Article  PubMed  CAS  Google Scholar 

  55. Hashimoto Y, Suzuki H, Aiso S, Niikura T, Nishimoto I, Matsuoka M (2005) Involvement of tyrosine kinases and STAT3 in Humanin-mediated neuroprotection. Life Sci 77:3092–3104

    Article  PubMed  CAS  Google Scholar 

  56. Guo B, Zhai D, Cabezas E, Welsh K, Nouraini S, Satterthwait AC, Reed JC (2003) Humanin peptide suppresses apoptosis by interfering with Bax activation. Nature 423:456–461

    Article  PubMed  CAS  Google Scholar 

  57. Ying G, Iribarren P, Zhou Y, Gong W, Zhang N, Yu ZX, Le Y, Cui Y, Wang JM (2004) Humanin, a newly identified neuroprotective factor, uses the G protein-coupled formylpeptide receptor-like-1 as a functional receptor. J Immunol 172:7078–7085

    PubMed  CAS  Google Scholar 

  58. Taga T (1997) gp130 and the interleukin-6 family of cytokines. Annu Rev Immunol 15:797–819

    Article  PubMed  CAS  Google Scholar 

  59. Heinrich C, Behrmann I, Haan S, Herrmanns H, Muller-newman G, Schaper F (2003) Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 374:1–20

    Article  PubMed  CAS  Google Scholar 

  60. Pflanz S, Hibbert L, Mattson J, Rosales R, Vaisberg E, Bazan J, Phillips J, McClanahan T, de Waal MR, Kastelein R (2004) WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27. J Immunol 172:2225–2231

    PubMed  CAS  Google Scholar 

  61. Takeda A, Hamano S, Yamanaka A, Hanada T, Ishibashi T, Mak TW, Yoshimura A, Yoshida H (2003) Role of IL-27/WSX-1 signaling for induction of T-bet through activation of STAT1 during initial Th1 commitment. J Immunol 170:4886–4890

    PubMed  CAS  Google Scholar 

  62. Kamiya S, Owaki T, Morishima N, Fukai F, Mizuguchi J, Yoshimoto T (2004) An indispensable role for STAT1 in IL-27-induced T-bet expression but not proliferation of naive CD4+ T cells. J Immunol 173:3871–3877

    PubMed  CAS  Google Scholar 

  63. Lucas S, Ghilardi N, Li J, de Sauvage FD (2003) IL-27 regulates IL-12 responsiveness of naive CD4+ T cells through Stat1-dependent and -independent mechanisms. Proc Natl Acad Sci USA 100:15047–15052

    Article  PubMed  CAS  Google Scholar 

  64. Yoshimura T, Takeda A, Hamano S, Miyazaki Y, Kinjyo I, Ishibashi T, Yoshimura Y, Yoshida H (2006) Two-sided roles of IL-27: induction of Th1 differentiation on naive CD4+ T cells versus suppression of proinflammatory cytokine production including IL-23-induced IL-17 on activated CD4+ T cells partially through STAT3-dependent mechanism. J Immunol 177:5377–5385

    PubMed  CAS  Google Scholar 

  65. Yoshida H, Yoshiyuki M (2008) Regulation of immune responses by interleukin-27. Immunol Rev 226:234–247

    Article  PubMed  CAS  Google Scholar 

  66. Stahl N, Davis S, Wong V, Taga T, Kishimoto T, Ip NY, Yancopoulos GD (1993) Cross-linking identifies leukemia inhibitory factor-binding protein as a ciliary neurotrophic factor receptor component. J Biol Chem 268:7628–7631

    PubMed  CAS  Google Scholar 

  67. Davis S, Aldrich TH, Stahl N, Pan L, Taga T, Kishimoto T, Ip NY, Yancopoulos GD (1993) LIFR beta and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor. Science 260:1805–1808

    Article  PubMed  CAS  Google Scholar 

  68. Elson GC, Lelievre E, Guillet C, Chevalier S, Plun-Favreau H, Froger J, Suard I, de Coignac AB, Delneste Y, Bonnefoy JY, Gauchat JF, Gascan H (2000) CLF associates with CLC to form a functional heteromeric ligand for the CNTF receptor complex. Nat Neurosci 3:867–872

    Article  PubMed  CAS  Google Scholar 

  69. Derouet D, Rousseau F, Alfonsi F, Froger J, Hermann J, Barbier F, Perret D, Diveu C, Guillet C, Preisser L, Dumont A, Barbado M, Morel A, deLapeyriere O, Gascan H, Chevalier S (2004) Neuropoietin, a new IL-6-related cytokine signaling through the ciliary neurotrophic factor receptor. Proc Natl Acad Sci USA 101:4827–4832

    Article  PubMed  CAS  Google Scholar 

  70. Niikura T, Yamada M, Chiba T, Aiso S, Matsuoka M, Nishimoto I (2004) Characterization of V642I-AbPP-induced cytotoxicity in primary neurons. J Neurosci Res 77:54–62

    Article  PubMed  CAS  Google Scholar 

  71. Hashimoto Y, Kurita M, Matsuoka M (2009) Identification of soluble WSX-1 not as a dominant-negative but as an alternative functional receptor subunit for an anti-Alzheimer’s disease rescue factor Humanin. Biochem Biophys Res Commun 389:95–99

    Article  PubMed  CAS  Google Scholar 

  72. Tajima H, Niikura T, Hashimoto Y, Ito Y, Kita Y, Terashita K, Yamazaki K, Koto A, Aiso S, Nishimoto I (2002) Evidence for in vivo production of Humanin peptide, a neuroprotective factor against Alzheimer’s disease-related insults. Neurosci Lett 324:227–231

    Article  PubMed  CAS  Google Scholar 

  73. Bodzioch M, Lapicka-Bodzioch K, Zapala B, Kamysz W, Kiec-Wilk B, Dembinska-Kiec A (2009) Evidence for potential functionality of nuclearly-encoded humanin isoforms. Genomics. 2 in press

  74. Wilcock GK, Black SE, Hendrix SB, Zavitz KH, Swabb EA, Laughlin MA (2008) Tarenflurbil Phase II Study investigators. Efficacy and safety of tarenflurbil in mild to moderate Alzheimer’s disease: a randomised phase II trial. Lancet Neurol 7:483–493

    Article  PubMed  CAS  Google Scholar 

  75. Terashita K, Hashimoto Y, Niikura T, Tajima H, Yamagishi Y, Ishizaka M, Kawasumi M, Chiba T, Kanekura K, Yamada M, Nawa M, Kita Y, Aiso S, Nishimoto I (2003) 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 85:1521–1538

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

We thank Dr. Ikuo Nishimoto, who passed away on October 17, 2003. We especially thank Ms. Takako Hiraki, for essential assistance. This work was supported by a grant from the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO).

Author information

Authors and Affiliations

  1. Department of Pharmacology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan

    Masaaki Matsuoka & Yuichi Hashimoto

Authors
  1. Masaaki Matsuoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuichi Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masaaki Matsuoka.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Matsuoka, M., Hashimoto, Y. Humanin and the Receptors for Humanin. Mol Neurobiol 41, 22–28 (2010). https://doi.org/10.1007/s12035-009-8090-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-009-8090-z

Keywords

Search

Navigation