Autophagy: A double-edged sword in Alzheimer's disease

Journal of biosciences

Hsinyu Lee⁴  Wen-Ming Hsu²  Bo-Jeng Wang³  Ming-Kuan Hu¹  Ying-Tsen Tung³  Wei-Pang Huang⁴  Yung-Feng Liao1 2³ 

[1] School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan$$;Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan$$;Laboratory of Molecular Neurobiology, Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan$$;Institute of Zoology, National Taiwan University, Taipei 10617, Taiwan$$

关键词: Alzheimer's disease;    amyloid precursor protein;    amyloid-ð?›½;    autophagy;    secretases;   

DOI  :  

来源: Indian Academy of Sciences

【 摘 要 】

Autophagy is a major protein degradation pathway that is essential for stress-induced and constitutive protein turnover. Accumulated evidence has demonstrated that amyloid-𝛽 (A𝛽) protein can be generated in autophagic vacuoles, promoting its extracellular deposition in neuritic plaques as the pathological hallmark of Alzheimer’s disease (AD). The molecular machinery for A𝛽 generation, including APP, APP-C99 and 𝛽-/𝛾-secretases, are all enriched in autophagic vacuoles. The induction of autophagy can be vividly observed in the brain at early stages of sporadic AD and in an AD transgenic mouse model. Accumulated evidence has also demonstrated a neuroprotective role of autophagy in mediating the degradation of aggregated proteins that are causative of various neurodegenerative diseases. Autophagy is thus widely regarded as an intracellular hub for the removal of the detrimental A𝛽 peptides and Tau aggregates. Nonetheless, compelling data also reveal an unfavorable function of autophagy in facilitating the production of intracellular A𝛽. The two faces of autophagy on the homeostasis of A𝛽 place it in a very unique and intriguing position in ADpathogenesis. This article briefly summarizes seminal discoveries that are shedding new light on the critical and unique roles of autophagy in AD and potential therapeutic approaches against autophagy-elicited AD.

【 授权许可】

Unknown