Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 113-122 |
| Number of pages | 10 |
| Journal | CNS Drug Reviews |
| Volume | 12 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2006 Jun 1 |
| Externally published | Yes |
Keywords
- β-Amyloid
- Alzheimer's disease
- Amyotrophic lateral sclerosis
- Colivelin
- Humanin
ASJC Scopus subject areas
- Pharmacology
- Neuropsychology and Physiological Psychology
Cite this
Humanin and colivelin : Neuronal-death-suppressing peptides for Alzheimer's disease and amyotrophic lateral sclerosis. / Matsuoka, Masaaki; Hashimoto, Yuichi; Aiso, Sadakazu; Nishimoto, Ikuo.
In: CNS Drug Reviews, Vol. 12, No. 2, 01.06.2006, p. 113-122.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Humanin and colivelin
T2 - Neuronal-death-suppressing peptides for Alzheimer's disease and amyotrophic lateral sclerosis
AU - Matsuoka, Masaaki
AU - Hashimoto, Yuichi
AU - Aiso, Sadakazu
AU - Nishimoto, Ikuo
PY - 2006/6/1
Y1 - 2006/6/1
N2 - 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.
AB - 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.
KW - β-Amyloid
KW - Alzheimer's disease
KW - Amyotrophic lateral sclerosis
KW - Colivelin
KW - Humanin
UR - http://www.scopus.com/inward/record.url?scp=33748049127&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748049127&partnerID=8YFLogxK
U2 - 10.1111/j.1527-3458.2006.00113.x
DO - 10.1111/j.1527-3458.2006.00113.x
M3 - Review article
C2 - 16958985
AN - SCOPUS:33748049127
VL - 12
SP - 113
EP - 122
JO - CNS Drug Reviews
JF - CNS Drug Reviews
SN - 1080-563X
IS - 2
ER -