Neuroscience Bulletin

, Volume 30, Issue 6, pp 923–935 | Cite as

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

  • Gao-Shang Chai
  • Dong-Xiao Duan
  • Rong-Hong Ma
  • Jian-Ying Shen
  • Hong-Lian Li
  • Zhi-Wei Ma
  • Yu Luo
  • Lu Wang
  • Xin-Hua Qi
  • Qun Wang
  • Jian-Zhi Wang
  • Zelan Wei
  • Darrell D. Mousseau
  • Li Wang
  • Gongping Liu
Original Article

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 

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Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Gao-Shang Chai
    • 1
    • 2
  • Dong-Xiao Duan
    • 1
    • 3
  • Rong-Hong Ma
    • 4
  • Jian-Ying Shen
    • 5
  • Hong-Lian Li
    • 5
  • Zhi-Wei Ma
    • 1
  • Yu Luo
    • 1
  • Lu Wang
    • 1
  • Xin-Hua Qi
    • 6
  • Qun Wang
    • 1
  • Jian-Zhi Wang
    • 1
  • Zelan Wei
    • 7
  • Darrell D. Mousseau
    • 7
  • Li Wang
    • 8
  • Gongping Liu
    • 1
  1. 1.Department of Pathophysiology, Key Laboratory of Neurological Diseases of Chinese Ministry of Education, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  2. 2.Department of Basic Medical, Wuxi Medical SchoolJiangnan UniversityWuxiChina
  3. 3.Department of Physiology, Basic Medical CollegeZhengzhou UniversityZhengzhouChina
  4. 4.Department of Laboratory Medicine, Union HospitalHuazhong University of Science and TechnologyWuhanChina
  5. 5.Department of Histology and Embryology, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  6. 6.Affiliated Hospital of Hebei University of EngineeringHandanChina
  7. 7.Department of Psychiatry, College of MedicineUniversity of SaskatchewanSaskatoonCanada
  8. 8.Department of PathophysiologyHenan Medical CollegeZhengzhouChina

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