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Humanin attenuates Alzheimer-like cognitive deficits and pathological changes induced by amyloid β-peptide in rats

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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.

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Authors and Affiliations

  1. 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

    Gao-Shang Chai, Dong-Xiao Duan, Zhi-Wei Ma, Yu Luo, Lu Wang, Qun Wang, Jian-Zhi Wang & Gongping Liu

  2. Department of Basic Medical, Wuxi Medical School, Jiangnan University, Wuxi, 214122, China

    Gao-Shang Chai

  3. Department of Physiology, Basic Medical College, Zhengzhou University, Zhengzhou, 450001, China

    Dong-Xiao Duan

  4. Department of Laboratory Medicine, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China

    Rong-Hong Ma

  5. Department of Histology and Embryology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Jian-Ying Shen & Hong-Lian Li

  6. Affiliated Hospital of Hebei University of Engineering, Handan, 056002, China

    Xin-Hua Qi

  7. Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5E5, Canada

    Zelan Wei & Darrell D. Mousseau

  8. Department of Pathophysiology, Henan Medical College, Zhengzhou, 451191, China

    Li Wang

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  1. Gao-Shang Chai
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  15. Gongping Liu
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Correspondence to Li Wang or Gongping Liu.

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Chai, GS., Duan, DX., Ma, RH. et al. Humanin attenuates Alzheimer-like cognitive deficits and pathological changes induced by amyloid β-peptide in rats. Neurosci. Bull. 30, 923–935 (2014). https://doi.org/10.1007/s12264-014-1479-3

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