Humanin is a small protein that can protect brain cells from the damage caused by amyloid‑beta, a key player in Alzheimer’s disease. It does this by turning on the JAK2/STAT3 signaling pathway, which keeps neurons healthy. As we age or develop disease, this pathway weakens, leading to memory problems, but boosting it with humanin or its stronger version, colivelin, may help preserve brain function.

Amyloid beta (Abeta) has long been implicated in the pathogenesis of Alzheimer's disease (AD). Little is known, however, about the intracellular events in neurons which lead to memory loss related to AD. Focusing on the fact that an AD-specific neuroprotective peptide named humanin (HN) inhibits AD-related neurotoxicity by activating the JAK2/STAT3 signaling axis, we recently found that age- and disease-dependent deterioration in the JAK2/STAT3 axis plays a critical role in the pathogenesis of AD. Here we summarize the neuroprotective effect of HN and its derivative, named colivelin (CLN), and also review the roles of the JAK2/STAT3 axis in memory impairment related to AD. The JAK2/STAT3 axis is a major transducer of HN-mediated neuroprotective activity. Abeta-dependent inactivation of the JAK2/STAT3 axis in hippocampal neurons causes cholinergic dysfunction via pre- and post-synaptic mechanisms, which leads to memory impairment related to AD. This provides not only a novel pathological hallmark of AD but also a novel target in AD therapy.