Humanin attenuates Alzheimer-like cognitive deficits and pathological changes induced by amyloid β-peptide in rats.
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 AD-like 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 Aβ(1-42). HN also attenuated Aβ(1-42)-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 Aβ(1-42). These findings provide novel mechanisms of action for the ability of HN to protect against Aβ(1-42)-induced AD-like pathological changes and memory deficits.
Department of Pathophysiology, Key Laboratory of Neurological Diseases of Chinese Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.|Department of Basic Medical, Wuxi Medical School, Jiangnan University, Wuxi, 214122, China.
Gao-Shang
GS
Chai
Department of Pathophysiology, Key Laboratory of Neurological Diseases of Chinese Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.|Department of Physiology, Basic Medical College, Zhengzhou University, Zhengzhou, 450001, China.
Dong-Xiao
DX
Duan
Department of Laboratory Medicine, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.
Rong-Hong
RH
Ma
Department of Histology and Embryology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Jian-Ying
JY
Shen
Department of Histology and Embryology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Hong-Lian
HL
Li
Department of Pathophysiology, Key Laboratory of Neurological Diseases of Chinese Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Zhi-Wei
ZW
Ma
Department of Pathophysiology, Key Laboratory of Neurological Diseases of Chinese Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Yu
Y
Luo
Department of Pathophysiology, Key Laboratory of Neurological Diseases of Chinese Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Lu
L
Wang
Affiliated Hospital of Hebei University of Engineering, Handan, 056002, China.
Xin-Hua
XH
Qi
Department of Pathophysiology, Key Laboratory of Neurological Diseases of Chinese Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Qun
Q
Wang
Department of Pathophysiology, Key Laboratory of Neurological Diseases of Chinese Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Jian-Zhi
JZ
Wang
Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5E5, Canada.
Zelan
Z
Wei
Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5E5, Canada.
Darrell D
DD
Mousseau
Department of Pathophysiology, Henan Medical College, Zhengzhou, 451191, China. kyk02@126.com.
Li
L
Wang
Department of Pathophysiology, Key Laboratory of Neurological Diseases of Chinese Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. liugp111@mail.hust.edu.cn.
Gongping
G
Liu
D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D016229:Amyloid beta-Peptides; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D003712:Dendrites / Q000187:drug effects* / Q000473:pathology; D049229:Dendritic Spines / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D047908:Intracellular Signaling Peptides and Proteins; C427211:humanin