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.