1Department of Pathophysiology, Key Laboratory of Neurological Diseases of Chinese Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
2Department of Basic Medical, Wuxi Medical School, Jiangnan University, Wuxi 214122, China
3Department of Physiology, Basic Medical College, Zhengzhou University, Zhengzhou 450001, China
4Department of Laboratory Medicine, Union Hospital, 5Department of Histology and Embryology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
6Affi liated Hospital of Hebei University of Engineering, Handan 056002, China
7Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5E5, Canada
8Department of Pathophysiology, Henan Medical College, Zhengzhou 451191, China
*These authors contributed equally to this work.

Abstract 

Amyloid β-peptide (Aβ) has been implicated as a key molecule in the neurodegenerative cascades of Alzheimer’s disease (AD). Humanin (HN) is a secretory peptide that inhibits the neurotoxicity of Aβ. However, the mechanism(s) by which HN exerts its neuroprotection against Aβ-induced ADlike pathological changes and memory deficits are yet to be completely defined. In the present study, we provided evidence that treatment of rats with HN increases the number of dendritic branches and the density of dendritic spines, and upregulates pre- and post-synaptic protein levels; these effects lead to enhanced long-term potentiation and amelioration of the memory deficits induced by Aβ1–42. HN also attenuated Aβ1–42-induced tau hyperphosphorylation, apparently by inhibiting the phosphorylation of Tyr307 on the inhibitory protein phosphatase-2A (PP2A) catalytic subunit and thereby activating PP2A. HN also inhibited apoptosis and reduced the oxidative stress induced by Aβ1–42. These findings provide novel mechanisms of action for the ability of HN to protect against Aβ1–42-induced AD-like pathological changes and memory deficits.

Keywords

Humanin; amyloid-beta; Alzheimer’s disease; tau; apoptosis

[SpringerLink]