humanin (HN, MT-RNR2)

Function

• role as a neuroprotective factor against death induced by multiple different types of familial Alzheimer disease genes & beta amyloid in Alzheimer disease
• induces chemotaxis of mononuclear phagocytes via FPRL1
• diminishes aggregation fibrillary formation
• suppresses effect of APP on mononuclear phagocytes
• competitively inhibits access of FPRL1 to APP
• prevents translocation of BAX from cytosol to mitochondria
• interacts with IGFBP3, BAX & TRIM11
• neuroprotection blocked by genistein (tyrosine kinase inhibitor)

Structure

• forms homodimer, essential for neuroprotection
  • Ser7 & Leu9 ?
• cDNA sequence 99% homologous to 16S mitochondrial ribosomal RNA

Compartment

secreted

Expression

• expressed in the heart, skeletal muscles, kidney, liver > brain, gastrointestinal tract
• release is regulated by intracellular mechanism
• intracellular level is regulated by TRIM11 through proteasomal pathway

Pathology

• expressed in AD brain, where it is found in some of the large intact neurons of the occipital lobes & small & round reactive glial cells in the hippocampus

Notes

• originally identified as neuroprotective against AD related neuronal cell death; found to suppress neuronal cell death induced by three FAD gene proteins:
  • amyloid precursor protein & A4 peptide
  • presenilin-1
  • presenilin-2

More general terms

• secreted peptide

Database

• OMIM: https://mirror.omim.org/entry/606120
• UniProt: http://www.uniprot.org/uniprot/Q8IVG9.html