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Modulation of autophagy as a therapeutic target for Alzheimer’s disease
     
 
John W. Steele, Emily Fan, Yildiz Kelahmetaglu, Yuan Tian, Victor Bustos

Rockefeller University.
Laboratory of Molecular and Cellular Neuroscience. Rockefeller University, New York, NY 10065
jsteele@rockefeller.edu

Macroautophagy(autophagy) is a conserved cellular pathway that regulates the degradation oflong-lived proteins, protein aggregates, and cellular organelles. Autophagy isessential for maintaining neuronal homeostasis; however, neuronal autophagicefficiency decreases with age. Therefore, aging is one of the greatest riskfactors for development of Alzheimer’s disease (AD), a slowly progressing formof neurodegeneration that develops over the course of 10-20 years prior to theonset of overt clinical symptoms. AD is defined neuropathologically by the presenceof extracellular aggregates of the amyloidogenic protein amyloid-b (Ab) and intracellularaccumulation of the microtubule-asssuggesting that an intimate association mayexist between neuronal autophagy stasis and Alzheimer’s-relatedpathology. Here,we highlight recent evidence that the autophagic pathway plays a role in boththe generation and clearance of the pathogenic Ab protein and its precursors.The primary focus of this review......

 
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