细胞外
神经科学
神经学
疾病
精神药理学
细胞内
阿尔茨海默病
医学
心理学
精神科
生物
内科学
细胞生物学
作者
Jan R. T. van Weering,Wiep Scheper
出处
期刊:CNS Drugs
[Springer Nature]
日期:2019-06-04
卷期号:33 (7): 639-648
被引量:26
标识
DOI:10.1007/s40263-019-00643-1
摘要
Disturbed proteostasis as reflected by a massive accumulation of misfolded protein aggregates is a central feature in Alzheimer's disease. Proteostatic disturbances may be caused by a shift in protein production and clearance. Whereas rare genetic causes of the disease affect the production side, sporadic cases appear to be directed by dysfunction in protein clearance. This review focusses on the involvement of lysosome-mediated clearance. Autophagy is a degradational system where intracellular components are degraded by lysosomal organelles. In addition, "outside-to-inside" trafficking through the endosomes converges with the autolysosomal pathway, thereby bringing together intracellular and extracellular components. Recent findings demonstrate that disturbance in the endo- and autolysosomal pathway induces "inside-to-outside" communication via induction of unconventional secretion, which may bear relevance to the spreading of disease pathology through the brain. The involvement of these pathways in the pathogenesis of the disease is discussed with an outlook to the opportunities it provides for diagnostics as well as therapeutic interventions.
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