The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration

被引:1048
作者
Heras-Sandoval, David [1 ]
Perez-Rojas, Jazmin M. [2 ]
Hernandez-Damian, Jacqueline [1 ]
Pedraza-Chaverri, Jose [1 ]
机构
[1] Univ Nacl Autonoma Mexico, Fac Quim, Dept Biol, Mexico City 04510, DF, Mexico
[2] Inst Nacl Cancerol, Mexico City, DF, Mexico
关键词
Phosphatidylinositol; 3; kinase; Mammalian target of rapamycin complex; Authophagy; Parkinson's disease; Alzheimer's disease; Neurodegeneration; FOCAL CEREBRAL-ISCHEMIA; CELL-DEATH; SIGNALING PATHWAY; MAMMALIAN TARGET; ALTERED DISTRIBUTION; HIPPOCAMPAL-NEURONS; PARKINSONS-DISEASE; UP-REGULATION; IN-VITRO; MTOR;
D O I
10.1016/j.cellsig.2014.08.019
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Disruption of autophagy plays an import role in neurodegenerative disorders, where deficient elimination of abnormal and toxic protein aggregates promotes cellular stress, failure and death. Therefore, induction of autophagy has been proposed as a reasonable strategy to help neurons clear abnormal protein aggregates and survive. The kinase mammalian target of rapamycin (mTOR) is a major regulator of the autophagic process and is regulated by starvation, growth factors, and cellular stressors. Upstream of mTOR the survival PI3K/AKT pathway modulates mTOR activity that is also altered in neurodegenerative diseases of Alzheimer and Parkinson. Nevertheless, the interplay between the PI3K/AKT/mTOR pathway and the autophagic process is complex and a more detailed examination of tissue from patients suffering neurodegenerative diseases and of animal and cellular models is needed. In the present work we review the recent findings on the role of the PI3K/AKT/mTOR pathway in the modulation of the autophagic process in neuronal protection. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:2694 / 2701
页数:8
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