The Role of PI3K/Akt and ERK in Neurodegenerative Disorders

被引：381

作者：

Rai, Sachchida Nand ^{[1
]}

Dilnashin, Hagera ^{[1
]}

Birla, Hareram ^{[1
]}

Sen Singh, Saumitra ^{[1
]}

Zahra, Walia ^{[1
]}

Rathore, Aaina Singh ^{[1
]}

Singh, Brijesh Kumar ^{[2
]}

Singh, Surya Pratap ^{[1
]}

机构：

[1] Banaras Hindu Univ, Inst Sci, Dept Biochem, Varanasi 221005, Uttar Pradesh, India

[2] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY 10032 USA

来源：

NEUROTOXICITY RESEARCH | 2019年 / 35卷 / 03期

关键词：

NDs; neurodegenerative disorders; MPTP; 1-methyl-4-phenyl-1; 2; 3; 6-tetrahydropyridine; 6-OHDA; 6-hydroxydopamine; PD; Parkinson's disease; HD; Huntington disease; BDNF; brain-derived neurotrophic factor; MAPK; mitogen-activated protein-extracellular kinase; Nrf2; nuclear factor erythroid 2 p45-related factor 2; ACTIVATED PROTEIN-KINASE; SIGNAL-REGULATED KINASE-5; INDUCED PARKINSONS-DISEASE; GROWTH-FACTOR RECEPTOR; NF-KAPPA-B; CELL-SURVIVAL; DOPAMINERGIC-NEURONS; HUNTINGTONS-DISEASE; MOUSE MODEL; PHOSPHATIDYLINOSITOL; 3-KINASE/AKT;

D O I：

10.1007/s12640-019-0003-y

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Disruption of Akt and Erk-mediated signal transduction significantly contributes in the pathogenesis of various neurodegenerative diseases (NDs), such as Parkinson's disease, Alzheimer's diseases, Huntington's disease, and many others. These regulatory proteins serve as the regulator of cell survival, motility, transcription, metabolism, and progression of the cell cycle. Therefore, targeting Akt and Erk pathway has been proposed as a reasonable approach to suppress ND progression. This review has emphasized on involvement of Akt/Erk cascade in the neurodegeneration. Akt has been reported to regulate neuronal toxicity through its various substrates like FOXos, GSK3, and caspase-9 etc. Akt is also involved with PI3K in signaling pathway to mediate neuronal survival. ERK is another kinase which also regulates proliferation, differentiation, and survival of the neural cell. There has also been much progress in developing a therapeutic molecule targeting Akt and Erk signaling. Therefore, improved understanding of the molecular mechanism behind the regulatory aspect of Akt and Erk networks can make strong impact on exploration of the neurodegenerative disease pathogenesis.

引用

页码：775 / 795

页数：21

共 172 条

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