A humanin derivative, S14G-HN, prevents amyloid-beta-induced memory impairment in mice.

Humanin (HN) is a 24-amino acid peptide that protects neuronal cells from death caused by Alzheimer's disease (AD)-related genes and amyloid-beta (Abeta). Multiple studies have revealed its biochemical and neuroprotective characteristics in vitro; however, little has been known regarding whether HN is effective in vivo in AD model systems. We examined the effect of S14G-HN, a 1,000-fold more potent derivative of HN in vitro, on amnesia induced by Abeta25-35 in mice. The Y-maze test revealed that at least 50 pmol of S14G-HN by intracerebroventricular injection prevented Abeta-induced impairment of short-term/spatial working memory; however, 5 nmol of S14A-HN, a neuroprotection-defective mutant in vitro, did not prevent Abeta-induced amnesia. These results are in agreement with the structure-function correlation shown previously in vitro. In the water-finding task, S14G-HN prevented prolongation of finding latency (the time to find water) observed in Abeta-amnesic mice, indicating that S14G-HN also blocked Abeta-induced impairment of latent learning. In accordance with these observations, immunohistochemical analysis showed that S14G-HN sustained the number of cholinergic neurons in the basal forebrain and the striata nearly to the normal level. Furthermore, genistein, a specific inhibitor of tyrosine kinases, blocked recovery from scopolamine-induced amnesia by S14G-HN, suggesting that certain tyrosine kinase(s) are involved in the inhibitory function of S14G-HN in vivo. Taking these findings together, we conclude that S14G-HN has rescue activity against memory impairment caused by AD-related insults in vivo by activating the same intracellular neuroprotective machinery as elucidated previously in vitro.

Tajima H ，Kawasumi M ，Chiba T ，Yamada M ，Yamashita K ，Nawa M ，Kita Y ，Kouyama K ，Aiso S ，Matsuoka M ，Niikura T ，Nishimoto I ... -  《JOURNAL OF NEUROSCIENCE RESEARCH》

Amyloid-beta causes memory impairment by disturbing the JAK2/STAT3 axis in hippocampal neurons.

Chiba T ，Yamada M ，Sasabe J ，Terashita K ，Shimoda M ，Matsuoka M ，Aiso S ... -  《-》

The multiple T-maze in vivo testing of the neuroprotective effect of humanin analogues.

Kunesová G ，Hlavácek J ，Patocka J ，Evangelou A ，Zikos C ，Benaki D ，Paravatou-Petsotas M ，Pelecanou M ，Livaniou E ，Slaninova J ... -  《PEPTIDES》

Differential susceptibility following beta-amyloid peptide-(1-40) administration in C57BL/6 and Swiss albino mice: Evidence for a dissociation between cognitive deficits and the glutathione system response.

Prediger RD ，Franco JL ，Pandolfo P ，Medeiros R ，Duarte FS ，Di Giunta G ，Figueiredo CP ，Farina M ，Calixto JB ，Takahashi RN ，Dafre AL ... -  《BEHAVIOURAL BRAIN RESEARCH》

A natural scavenger of peroxynitrites, rosmarinic acid, protects against impairment of memory induced by Abeta(25-35).

Alkam T ，Nitta A ，Mizoguchi H ，Itoh A ，Nabeshima T ... -  《BEHAVIOURAL BRAIN RESEARCH》