Open AccessHumanin and Colivelin: Neuronal‐Death‐Suppressing Peptides for Alzheimer's Disease and Amyotrophic Lateral Sclerosis
Author(s) -
Matsuoka Masaaki,
Hashimoto Yuichi,
Aiso Sadakazu,
Nishimoto Ikuo
Publication year - 2006
Publication title -
cns drug reviews
Language(s) - English
Resource type - Journals
eISSN - 1527-3458
pISSN - 1080-563X
DOI - 10.1111/j.1527-3458.2006.00113.x
Subject(s) - neuroprotection , amyotrophic lateral sclerosis , sod1 , programmed cell death , in vivo , pharmacology , neurotrophic factors , medicine , neurotrophin , microbiology and biotechnology , neuroscience , chemistry , biochemistry , receptor , biology , disease , apoptosis
Humanin (HN), a 24‐amino‐acid neuroprotective peptide, was originally found in the occipital lobe of an autopsied Alzheimer's disease (AD) patient. HN inhibits neuronal death by binding to its specific receptor on the cell membrane and triggering a Jak2/STAT3 prosurvival pathway. The activation of this pathway may represent a therapeutic approach to AD. HN also exhibits neuroprotective activity against toxicity by familial amyotrophic lateral sclerosis (ALS)‐related mutant superoxide dismutase (SOD1). Recent investigations established that AGA‐(C8R)‐HNG17, a 17‐amno‐acid derivative of HN, is 10 5 times more potent as a neuroprotective than HN; at 10‐picomolar and higher concentrations in vitro it completely suppresses neuronal death. Moreover, a 26‐amino‐acid peptide colivelin (CL), composed of activity‐dependent neurotrophic factor (ADNF) C‐terminally fused to AGA‐(C8R)‐HNG17, provides complete neuroprotection at 100‐femtomolar or higher concentrations in vitro. A series of experiments using mouse AD and ALS models further established the efficacy of HN derivatives, including CL, against these diseases in vivo. HN and CL can be viewed as drug candidates for neuronal death suppression therapy in AD or ALS.