Targeting PI3K-AKT/mTOR signaling in the prevention of autism

被引:87
作者
Sharma, Aarti [1 ]
Mehan, Sidharth [1 ]
机构
[1] ISF Coll Pharm, Dept Pharmacol, Neuropharmacol Div, Moga 142001, Punjab, India
关键词
Autism; PI3K-AKT; mTOR; Apoptosis; Serotonergic degeneration; Genetic dysfunction; MITOCHONDRIAL DYSFUNCTION; SYNAPTIC PLASTICITY; HUNTINGTONS-DISEASE; TUBEROUS SCLEROSIS; MAMMALIAN TARGET; MOUSE MODEL; PHOSPHATIDYLINOSITOL; 3-KINASE; SPECTRUM DISORDERS; THERAPEUTIC TARGET; PROTEIN-SYNTHESIS;
D O I
10.1016/j.neuint.2021.105067
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
PI3K-AKT/mTOR signaling pathway represents an essential signaling mechanism for mammalian enzyme-related receptors in transducing signals or biological processes such as cell development, differentiation, cell survival, protein synthesis, and metabolism. Upregulation of the PI3K-AKT/mTOR signaling pathway involves many human brain abnormalities, including autism and other neurological dysfunctions. Autism is a neurodevelopmental disorder associated with behavior and psychiatric illness. This research-based review discusses the functional relationship between the neuropathogenic factors associated with PI3K-AKT/mTOR signaling pathway. Ultimately causes autism-like conditions associated with genetic alterations, neuronal apoptosis, mitochondrial dysfunction, and neuroinflammation. Therefore, inhibition of the PI3K-AKT/mTOR signaling pathway may have an effective therapeutic value for autism treatment. The current review also summarizes the involvement of PI3K-AKT/mTOR signaling pathway inhibitors in the treatment of autism and other neurodegenerative disorders.
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收藏
页数:15
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共 229 条
[1]   Serotonin and serotonin transporter levels in autistic children [J].
Abdulamir, Haidar A. ;
Abdul-Rasheed, Omar F. ;
Abdulghani, Emad A. .
SAUDI MEDICAL JOURNAL, 2018, 39 (05) :487-494
[2]   Phosphatidylinositol 3-Kinase Facilitates Microtubule-dependent Membrane Transport for Neuronal Growth Cone Guidance [J].
Akiyama, Hiroki ;
Kamiguchi, Hiroyuki .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (53) :41740-41748
[3]   Pten Deletion in Adult Hippocampal Neural Stem/Progenitor Cells Causes Cellular Abnormalities and Alters Neurogenesis [J].
Amiri, Anahita ;
Cho, Woosung ;
Zhou, Jing ;
Birnbaum, Shari G. ;
Sinton, Christopher M. ;
McKay, Renee M. ;
Parada, Luis F. .
JOURNAL OF NEUROSCIENCE, 2012, 32 (17) :5880-5890
[4]   Serotonin transporter availability in adults with autism-a positron emission tomography study [J].
Andersson, Max ;
Tangen, Amma ;
Farde, Lars ;
Bolte, Sven ;
Halldin, Christer ;
Borg, Jacqueline ;
Lundberg, Johan .
MOLECULAR PSYCHIATRY, 2021, 26 (05) :1647-1658
[5]   mTOR signaling regulates the morphology and migration of outer radial glia in developing human cortex [J].
Andrews, Madeline G. ;
Subramanian, Lakshmi ;
Kriegstein, Arnold R. .
ELIFE, 2020, 9
[6]  
[Anonymous], 2020, J NEUROCHEM, DOI DOI 10.1111/JNC.15152
[7]   Mutations causing syndromic autism define an axis of synaptic pathophysiology [J].
Auerbach, Benjamin D. ;
Osterweil, Emily K. ;
Bear, Mark F. .
NATURE, 2011, 480 (7375) :63-U222
[8]   Microglia in Neurological Diseases: A Road Map to Brain-Disease Dependent-Inflammatory Response [J].
Bachiller, Sara ;
Jimenez-Ferrer, Itzia ;
Paulus, Agnes ;
Yang, Yiyi ;
Swanberg, Maria ;
Deierborg, Tomas ;
Boza-Serrano, Antonio .
FRONTIERS IN CELLULAR NEUROSCIENCE, 2018, 12
[9]   Lack of association of rare functional variants in TSC1/TSC2 genes with autism spectrum disorder [J].
Bahl, Samira ;
Chiang, Colby ;
Beauchamp, Roberta L. ;
Neale, Benjamin M. ;
Daly, Mark J. ;
Gusella, James F. ;
Talkowski, Michael E. ;
Ramesh, Vijaya .
MOLECULAR AUTISM, 2013, 4
[10]   Mitochondrial dysfunction: A hidden trigger of autism? [J].
Balachandar, Vellingiri ;
Rajagopalan, Kamarajan ;
Jayaramayya, Kaavya ;
Jeevanandam, Madesh ;
Iyer, Mahalaxmi .
GENES & DISEASES, 2021, 8 (05) :629-639