title: Autophagy: a double-edged sword in Alzheimer's disease.
abstract: Autophagy is a major protein degradation pathway that is essential for stress-induced and constitutive protein turnover. Accumulated evidence has demonstrated that amyloid-beta (A beta) 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 A beta generation, including APP, APP-C99 and beta-/gamma-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 A beta peptides and Tau aggregates. Nonetheless, compelling data also reveal an unfavorable function of autophagy in facilitating the production of intracellular A beta. The two faces of autophagy on the homeostasis of A beta place it in a very unique and intriguing position in AD pathogenesis. 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.
authors.affiliation: Laboratory of Molecular Neurobiology, Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Ying-Tsen
authors.initials: YT
authors.lastname: Tung
authors.forename: Bo-Jeng
authors.initials: BJ
authors.lastname: Wang
authors.forename: Ming-Kuan
authors.initials: MK
authors.lastname: Hu
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Hsu
authors.forename: Hsinyu
authors.initials: H
authors.lastname: Lee
authors.forename: Wei-Pang
authors.initials: WP
authors.lastname: Huang
authors.forename: Yung-Feng
authors.initials: YF
authors.lastname: Liao
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D059748:Proteolysis; D014617:Vacuoles / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins