Abstract: One aspect of the present invention is directed to search receptors based on the information of HN signaling pathways in order to find Humanin receptor or Humanin-like polypeptide receptor (HNR), and to reveal a mechanism of promoting or suppressing the intracellular signal transduction for neuroprotecting activity of HN and identify a compound involved in the mechanism. The aspect of the invention is directed to a method for screening of HNR agonist and HNR antagonist, to utilize the screened compound in development of a drug for the treatment of neurodegenerative disease, and to provide an assay system of AD neuronal cell death, and to provide methods for the compulsory expression of HNR gene or knocking-out of intracellular genes.

Abstract: The present invention relates to a pharmaceutical composition for the treatment and/or prevention of a neurodegenerative disease, comprising the following polypeptide shown in any of (a) to (c): (a) a polypeptide comprising the amino acid sequence represented by Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala-Pro-Ala-Gly-Ala-Ser-Arg-Leu-Leu-Leu-Leu-Thr-Gly-Glu-Ile-Asp-Leu-Pro (SEQ ID NO: 1); (b) a polypeptide comprising an amino acid sequence having a deletion, substitution, insertion, and/or addition of one or several amino acids in the amino acid sequence consisting of Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala-Pro-Ala-Gly-Ala-Ser-Arg-Leu-Leu-Leu-Leu-Thr-Gly-Glu-Ile-Asp-Leu-Pro (SEQ ID NO: 1), and having an activity that inhibits neuronal cell death associated with neurodegenerative disease; and (c) a modified polypeptide from the polypeptide (a) or (b), or a pharmaceutically acceptable salt thereof, as an effective ingredient.