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Review

Reducing PDK1/Akt Activity: An Effective Therapeutic Target in the Treatment of Alzheimer’s Disease

College of Life Sciences, Northwest Normal University, Lanzhou 730070, China
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Author to whom correspondence should be addressed.
Academic Editors: Jeyanthy Eswaran and Meera Soundararajan
Cells 2022, 11(11), 1735; https://doi.org/10.3390/cells11111735
Received: 5 April 2022 / Revised: 16 May 2022 / Accepted: 24 May 2022 / Published: 24 May 2022
(This article belongs to the Special Issue Protein Kinases and Neurodegeneration)
Alzheimer’s disease (AD) is a common age-related neurodegenerative disease that leads to memory loss and cognitive function damage due to intracerebral neurofibrillary tangles (NFTs) and amyloid-β (Aβ) protein deposition. The phosphoinositide-dependent protein kinase (PDK1)/protein kinase B (Akt) signaling pathway plays a significant role in neuronal differentiation, synaptic plasticity, neuronal survival, and neurotransmission via the axon–dendrite axis. The phosphorylation of PDK1 and Akt rises in the brain, resulting in phosphorylation of the TNF-α-converting enzyme (TACE) at its cytoplasmic tail (the C-terminal end), changing its internalization as well as its trafficking. The current review aimed to explain the mechanisms of the PDK1/Akt/TACE signaling axis that exerts its modulatory effect on AD physiopathology. We provide an overview of the neuropathological features, genetics, Aβ aggregation, Tau protein hyperphosphorylation, neuroinflammation, and aging in the AD brain. Additionally, we summarized the phosphoinositide 3-kinase (PI3K)/PDK1/Akt pathway-related features and its molecular mechanism that is dependent on TACE in the pathogenesis of AD. This study reviewed the relationship between the PDK1/Akt signaling pathway and AD, and discussed the role of PDK1/Akt in resisting neuronal toxicity by suppressing TACE expression in the cell membrane. This work also provides a perspective for developing new therapeutics targeting PDK1/Akt and TACE for the treatment of AD. View Full-Text
Keywords: Alzheimer’s disease; amyloid-β; Tau; 3-phosphoinositide dependent kinase 1; protein kinase B; phosphoinositide 3-kinase; TNF-α converting enzyme Alzheimer’s disease; amyloid-β; Tau; 3-phosphoinositide dependent kinase 1; protein kinase B; phosphoinositide 3-kinase; TNF-α converting enzyme
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MDPI and ACS Style

Yang, S.; Du, Y.; Zhao, X.; Wu, C.; Yu, P. Reducing PDK1/Akt Activity: An Effective Therapeutic Target in the Treatment of Alzheimer’s Disease. Cells 2022, 11, 1735. https://doi.org/10.3390/cells11111735

AMA Style

Yang S, Du Y, Zhao X, Wu C, Yu P. Reducing PDK1/Akt Activity: An Effective Therapeutic Target in the Treatment of Alzheimer’s Disease. Cells. 2022; 11(11):1735. https://doi.org/10.3390/cells11111735

Chicago/Turabian Style

Yang, Shaobin, Yaqin Du, Xiaoqian Zhao, Chendong Wu, and Peng Yu. 2022. "Reducing PDK1/Akt Activity: An Effective Therapeutic Target in the Treatment of Alzheimer’s Disease" Cells 11, no. 11: 1735. https://doi.org/10.3390/cells11111735

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