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

被引：89

作者：

Sharma, Aarti ^{[1
]}

Mehan, Sidharth ^{[1
]}

机构：

[1] ISF Coll Pharm, Dept Pharmacol, Neuropharmacol Div, Moga 142001, Punjab, India

来源：

NEUROCHEMISTRY INTERNATIONAL | 2021年 / 147卷

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.

引用

页数：15

共 229 条

[21] Epidemiology of Autism Spectrum Disorders in Adults in the Community in England [J].

Brugha, Traolach S. ;

McManus, Sally ;

Bankart, John ;

Scott, Fiona ;

Purdon, Susan ;

Smith, Jane ;

Bebbington, Paul ;

Jenkins, Rachel ;

Meltzer, Howard .

ARCHIVES OF GENERAL PSYCHIATRY, 2011, 68 (05) :459-466

[22] The Prevalence and Impact of Hyperglycemia and Hyperlipidemia in Patients With Advanced Cancer Receiving Combination Treatment With the Mammalian Target of Rapamycin Inhibitor Temsirolimus and Insulin Growth Factor-Receptor Antibody Cixutumumab [J].

Busaidy, Naifa L. ;

Lorusso, Patricia ;

Lawhorn, Kristie ;

Hess, Kenneth R. ;

Habra, Mohammed Amir ;

Fu, Siqing ;

Hong, Ddavid S. ;

Chen, Helen X. ;

Doyle, Lawrence A. ;

Kurzrock, Razelle ;

Naing, Aung .

ONCOLOGIST, 2015, 20 (07) :737-741

[23] Neurobehavioral phenotype of autism spectrum disorder associated with germline heterozygous mutations in PTEN [J].

Busch, Robyn M. ;

Srivastava, Siddharth ;

Hogue, Olivia ;

Frazier, Thomas W. ;

Klaas, Patricia ;

Hardan, Antonio ;

Martinez-Agosto, Julian A. ;

Sahin, Mustafa ;

Eng, Charis ;

Warfield, Simon K. ;

Scherrer, Benoit ;

Dies, Kira ;

Filip-Dhima, Rajna ;

Gulsrud, Amanda ;

Hanson, Ellen ;

Phillips, Jennifer M. .

TRANSLATIONAL PSYCHIATRY, 2019, 9 (1)

[24] Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly [J].

Buxbaum, Joseph D. ;

Cai, Guiqing ;

Chaste, Pauline ;

Nygren, Gudrun ;

Goldsmith, Juliet ;

Reichert, Jennifer ;

Anckarsater, Henrik ;

Rastam, Maria ;

Smith, Christopher J. ;

Silverman, Jeremy M. ;

Hollander, Eric ;

Leboyer, Marion ;

Gillberg, Christopher ;

Verloes, Alain ;

Betancur, Catalina .

AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2007, 144B (04) :484-491

[25] EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy [J].

Byrne, Susan ;

Jansen, Lara ;

U-King-Im, Jean-Marie ;

Siddiqui, Ata ;

Lidov, Hart G. W. ;

Bodi, Istvan ;

Smith, Luke ;

Mein, Rachael ;

Cullup, Thomas ;

Dionisi-Vici, Carlo ;

Al-Gazali, Lihadh ;

Al-Owain, Mohammed ;

Bruwer, Zandre ;

Al Thihli, Khalid ;

El-Garhy, Rana ;

Flanigan, Kevin M. ;

Manickam, Kandamurugu ;

Zmuda, Erik ;

Banks, Wesley ;

Gershoni-Baruch, Ruth ;

Mandel, Hanna ;

Dagan, Efrat ;

Raas-Rothschild, Annick ;

Barash, Hila ;

Filloux, Francis ;

Creel, Donnell ;

Harris, Michael ;

Hamosh, Ada ;

Koelker, Stefan ;

Ebrahimi-Fakhari, Darius ;

Hoffmann, Georg F. ;

Manchester, David ;

Boyer, Philip J. ;

Manzur, Adnan Y. ;

Lourenco, Charles Marques ;

Pilz, Daniela T. ;

Kamath, Arveen ;

Prabhakar, Prab ;

Rao, Vamshi K. ;

Rogers, R. Curtis ;

Ryan, Monique M. ;

Brown, Natasha J. ;

McLean, Catriona A. ;

Said, Edith ;

Schara, Ulrike ;

Stein, Anja ;

Sewry, Caroline ;

Travan, Laura ;

Wijburg, Frits A. ;

Zenker, Martin .

BRAIN, 2016, 139 :765-781

[26] Wortmannin Attenuates Seizure-Induced Hyperactive PI3K/Akt/mTOR Signaling, Impaired Memory, and Spine Dysmorphology in Rats [J].

Carter, Angela N. ;

Born, Heather A. ;

Levine, Amber T. ;

Dao, An T. ;

Zhao, Amanda J. ;

Lee, Wai L. ;

Anderson, Anne E. .

ENEURO, 2017, 4 (03)

[27] Downregulated AKT-mTOR signaling pathway proteins in dorsolateral prefrontal cortex in Schizophrenia [J].

Chadha, Radhika ;

Meador-Woodruff, James H. .

NEUROPSYCHOPHARMACOLOGY, 2020, 45 (06) :1059-1067

[28] MeCP2 controls excitatory synaptic strength by regulating glutamatergic synapse number [J].

Chao, Hsiao-Tuan ;

Zoghbi, Huda Y. ;

Rosenmund, Christian .

NEURON, 2007, 56 (01) :58-65

[29] Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes [J].

Chao, Hsiao-Tuan ;

Chen, Hongmei ;

Samaco, Rodney C. ;

Xue, Mingshan ;

Chahrour, Maria ;

Yoo, Jong ;

Neul, Jeffrey L. ;

Gong, Shiaoching ;

Lu, Hui-Chen ;

Heintz, Nathaniel ;

Ekker, Marc ;

Rubenstein, John L. R. ;

Noebels, Jeffrey L. ;

Rosenmund, Christian ;

Zoghbi, Huda Y. .

NATURE, 2010, 468 (7321) :263-269

[30] Dysregulation of the IGF-I/PI3K/AKT/mTOR signaling pathway in autism spectrum disorders [J].

Chen, Jianling ;

Alberts, Ian ;

Li, Xiaohong .

INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, 2014, 35 :35-41

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