Anti‐amyloid activity of neprilysin in plaque‐bearing mouse models of Alzheimer's disease

FEBS Letters

Kuehnle, Katrin¹  Nitsch, Roger M.¹  Poirier, Raphael¹  Li, Hong¹  Tracy, Jay¹  Mohajeri, M.Hasan¹ 

[1] Division of Psychiatry Research, University of Zurich, August Forel Str. 1, 8008 Zurich, Switzerland

关键词: Transgenic mouse;    Alzheimer's disease;    β-Amyloid peptide;    Protein stability;    Therapy;    Neprilysin;    Aβ;    β-amyloid peptide;    AD;    Alzheimer's disease;    APP;    amyloid precursor protein;    NEP;    neprilysin;    Iba-1;    ionized calcium binding adapter molecule 1;    GFAP;    glial fibrillary acidic protein;   

DOI  :  10.1016/S0014-5793(04)00169-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Abnormally high concentrations of β-amyloid peptide (Aβ) and amyloid plaque formation in Alzheimer's disease (AD) may be caused either by increased generation or by decreased degradation of Aβ. Therefore, activation of mechanisms that lower brain Aβ levels is considered valuable for AD therapy. Neuronal upregulation of neprilysin (NEP) in young transgenic mice expressing the AD-causing amyloid precursor protein mutations (SwAPP) led to reduction of brain Aβ levels and delayed Aβ plaque deposition. In contrast, a comparable increase of brain NEP levels in aged SwAPP mice with pre-existing plaque pathology did not result in a significant reduction of plaque pathology. Therefore, we suggest that the potential of NEP for AD therapy is age-dependent and most effective early in the course of AD pathophysiology.

【 授权许可】

Unknown