Autophagic/lysosomal dysfunction in Alzheimer's disease

被引:156
作者
Orr, Miranda E. [1 ,2 ]
Oddo, Salvatore [1 ,2 ,3 ,4 ]
机构
[1] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA
[2] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA
[3] Univ Arizona, Coll Med Phoenix, Banner Sun Hlth Res Inst, Sun City, AZ 85351 USA
[4] Univ Arizona, Coll Med Phoenix, Dept Basic Med Sci, Sun City, AZ 85351 USA
基金
美国国家卫生研究院;
关键词
AMYLOID-BETA DEPOSITION; CYSTATIN C GENE; CATHEPSIN-B; MOUSE MODEL; NEURONAL AUTOPHAGY; MAMMALIAN TARGET; WILD-TYPE; MTOR; PRESENILIN; MECHANISMS;
D O I
10.1186/alzrt217
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Autophagy serves as the sole catabolic mechanism for degrading organelles and protein aggregates. Increasing evidence implicates autophagic dysfunction in Alzheimer's disease (AD) and other neurodegenerative diseases associated with protein misprocessing and accumulation. Under physiologic conditions, the autophagic/lysosomal system efficiently recycles organelles and substrate proteins. However, reduced autophagy function leads to the accumulation of proteins and autophagic and lysosomal vesicles. These vesicles contain toxic lysosomal hydrolases as well as the proper cellular machinery to generate amyloid-beta, the major component of AD plaques. Here, we provide an overview of current research focused on the relevance of autophagic/lysosomal dysfunction in AD pathogenesis as well as potential therapeutic targets aimed at restoring autophagic/lysosomal pathway function.
引用
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页数:9
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