Humanin

Humanin is a 24-amino-acid peptide (MAPRGFSCLLLLTSEIDLPVKRRA; C119H204N34O32S2, 2,687.2 g/mol) classed as a mitochondrial-derived peptide because it is encoded within mitochondrial DNA. It was identified in 2001 through a functional expression screen for cDNAs that suppress neuronal cell death in culture; the transfected cDNA was transcribed into the corresponding polypeptide, which was secreted into the culture medium, and its activity depended on its primary structure. Humanin has since been detected in several tissues with high metabolic rates, including glial cells of the brain.

Humanin in the research literature

Two receptor systems have been described for humanin. In cell-based binding and loss-of-function studies, the peptide induced hetero-oligomerization of ciliary neurotrophic factor receptor alpha (CNTFR), the IL-27 receptor subunit WSX-1 and gp130, with STAT3 activation implicated downstream. Separately, humanin suppressed forskolin-induced cAMP production in CHO cells expressing formyl peptide receptor-like 1 (FPRL1) or FPRL2, and an N-formylated form was markedly more potent at FPRL1. Reviews also describe JAK/STAT signaling and interactions with BCL-2 family proteins.

In rat hippocampus, humanin immunoreactivity colocalized with astroglial markers, and cultured astrocytes were shown to produce and release the peptide. In primary cultures of hippocampal neurons, humanin reduced glutamate-induced dendritic atrophy and the loss of synaptophysin-positive puncta.