Humanin is a novel neuroprotective agent against stroke.
Xu. Xingshun X; Chua. Chu C CC; Gao. Jinping J; Hamdy. Ronald C RC; Chua. Balvin H L BH
Key Findings
- A single low dose of HNG given directly into the brain before a stroke reduced brain damage by more than half
- Giving HNG up to 4 hours after the stroke still lowered damage and improved function
- HNG’s protection was linked to less cell death and reduced activation of the ERK pathway
Practical Outcomes
- While the results are promising, the study used invasive brain injections in mice, so there’s no ready‑to‑use protocol for people. It suggests that boosting humanin levels might someday help protect the brain from stroke, but more research and safe delivery methods are needed before biohackers can apply it.
Summary
In mice, a powerful form of the tiny protein humanin (called HNG) given before or shortly after a stroke‑like brain injury dramatically cut the amount of brain damage and improved neurological scores. The protection seems to involve blocking a stress‑signalling pathway (ERK).
Abstract
Humanin (HN) is a 24-amino acid peptide best known for its ability to protect neurons from damage caused by Alzheimer disease-related proteins. This study examines the neuroprotective effects of HNG (a potent form of HN) on focal cerebral ischemia/reperfusion injury in mice. Mice underwent middle cerebral artery occlusion for 75 minutes followed by 24-hour reperfusion. Mice were pretreated with 0.1 microg HNG (intracerebroventricularly) 30 minutes before ischemia; posttreated at 0, 2, 4, and 6 hours after ischemia; or pretreated with 1 microg HNG (intraperitoneally) 1 hour before ischemia. Neurological deficits and cerebral infarct volume were evaluated. Neuronal apoptosis and activated poly(ADP-ribose) polymerase expression were measured by TUNEL and Western blot analysis, respectively. Activated ERKs were examined by Western blot analysis. Pretreatment with 0.1 microg HNG (intracerebroventricularly) 30 minutes before ischemia reduced cerebral infarct volume from 56.2+/-3.0% to 26.1+/-1.4% (P<0.01). HNG posttreatment after 4 hours of reperfusion reduced cerebral infarct volume to 45.6+/-2.6% (P<0.05). Pretreatment with 1 microg HNG (intraperitoneally) 1 hour before ischemia or posttreatment after 2 hours of reperfusion reduced cerebral infarct volume significantly. HNG also significantly improved neurological function and inhibited both neuronal apoptosis as well as poly(ADP-ribose) polymerase activation. A significant decrease of phospho-ERK was observed in mice treated with HNG, whereas phospho-JNK and phospho-p38 levels were not altered. Our results demonstrate that HNG protects against cerebral ischemia/reperfusion injury in mice. HNG offers neuroprotection in vivo at least in part by inhibiting ERK activation. These findings suggest a potential therapeutic role for HNG in the treatment of stroke.
Study Information
pubmed
2006
2006-09-07T00:00:00.000Z
10.1161/01.str.0000242772.94277.1f