Humanin: a potential peptide for neuroprotective therapy against Alzheimer's disease

Abstract

Neuronal cell death is a pathologic hallmark of Alzheimer's disease (AD), a devastating neurodegenerative disorder. To understand the cytotoxic mechanism underlying AD pathogenesis, a functional screen termed the ‘disease-based death trap’ has been used. This method was developed to identify antagonistic genes against neuronal cell death caused by an AD-associated insult. Among several antagonistic genes obtained, a cDNA was found that encodes a novel 24-residue peptide, which was later designated humanin (HN). The synthetic HN peptide suppresses neuronal cell death induced by all AD-related insults so far examined, including amyloid β in vitro. A highly potent HN derivative ameliorates amnesia in an AD mouse model, suggesting that therapy involving HN effectively targets neuronal death in AD.

Keywords::

• Alzheimer's disease
• amyloid β
• amyloid precursor protein
• cDNA library
• cell death
• humanin
• neuroprotection
• presenilin
• screening

Acknowledgement

The author dedicates this article to the late Professor Ikuo Nishimoto (1956 – 2003) who had led the project described here. The author thanks former members of the team, particularly Y Hashimoto, H Tajima, T Yasukawa, Y Ito, N Murayama and M Kawasumi for their contributions to this project, and finally D Wylie for expert assistance.

Notes