mTOR signalling pathway - A root cause for idiopathic autism?
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Autism spectrum disorder (ASD) is a complex neurodevelopmental monogenic disorder with a strong genetic influence. Idiopathic autism could be defined as a type of autism that does not have a specific causative agent. Among signalling cascades, mTOR signalling pathway plays a pivotal role not only in cell cycle, but also in protein synthesis and regulation of brain homeostasis in ASD patients. The present review highlights, underlying mechanism of mTOR and its role in altered signalling cascades as a triggering factor in the onset of idiopathic autism. Further, this review discusses how distorted mTOR signalling pathway stimulates truncated translation in neuronal cells and leads to downregulation of protein synthesis at dendritic spines of the brain. This review concludes by suggesting downstream regulators such as p70S6K, eIF4B, eIF4E of mTOR signalling pathway as promising therapeutic targets for idiopathic autistic individuals.
Abstract
Autism spectrum disorder (ASD) is a complex neurodevelopmental monogenic disorder with a strong genetic influence. Idiopathic autism could be defined as a type of autism that does not have a specific causative agent. Among signalling cascades, mTOR signalling pathway plays a pivotal role not only in cell cycle, but also in protein synthesis and regulation of brain homeostasis in ASD patients. The present review highlights, underlying mechanism of mTOR and its role in altered signalling cascades as a triggering factor in the onset of idiopathic autism. Further, this review discusses how distorted mTOR signalling pathway stimulates truncated translation in neuronal cells and leads to downregulation of protein synthesis at dendritic spines of the brain. This review concludes by suggesting downstream regulators such as p70S6K, eIF4B, eIF4E of mTOR signalling pathway as promising therapeutic targets for idiopathic autistic individuals.
참고문헌 (92)
- Al-Zahrani A, "Prevalence and clinical characteristics of autism spectrum disorders in school-age children in Taif-KSA", Int J Med Sci Public Health, 2, pp.578~582 (2013)
- Gilbert J, "Fundamental elements in autism : from neurogenesis and neurite growth to synaptic plasticity", Front Cell Neurosci, 11, pp.359~ (2017)
- Jiang YH, "Genetic diagnosis of autism spectrum disorders : the opportunity and challenge in the genomics era", Crit Rev Clin Lab Sci, 51, pp.249~262 (2014)
- Mattila ML, "Autism spectrum disorders according to DSM-IV-TR and comparison with DSM-5 draft criteria : an epidemiological study", J Am Acad Child Adolesc Psychiatry, 50, pp.583~592 (2011)
- Harker CM, "Comparison of the Diagnostic Criteria for Autism Spectrum Disorder Across DSM-5, DSM-IV-TR, 2 and the Individuals with Disabilities Act (IDEA) 3 Definition of Autism", 1~6 (2014)
- King BH, "Update on diagnostic classification in autism", Curr Opin Psychiatry, 27, pp.105~ (2014)
- Howes OD, "Autism spectrum disorder : Consensus guidelines on assessment, treatment and research from the British Association for Psychopharmacology", J Psychopharmacol, 32, pp.3~29 (2018)
- Venugopal A, "Monogenic diseases in India", Mutat Res, 776, pp.23~31 (2018)
- Nicolini C, "Decreased mTOR signaling pathway in human idiopathic autism and in rats exposed to valproic acid", Acta Neuropathol Commun, 3, pp.3~ (2015)
- Sandin S, "The familial risk of autism", JAMA, 311, pp.1770~1777 (2014)
- Berko ER, "Mosaic epigenetic dysregulation of ectodermal cells in autism spectrum disorder", PLoS Genet, 10, pp.e1004402~ (2014)
- St-Hilaire S, "An ecological study on childhood autism", Int J of Health Geogr, 11, pp.44~ (2012)
- Tordjman S, "Autism as a disorder of biological and behavioral rhythms : toward new therapeutic perspectives", Front Pediatr, 3, pp.1~ (2015)
- Volk HE, "Traffic-related air pollution, particulate matter, and autism", JAMA Psychiatry, 70, pp.71~77 (2013)
- Subramanian M, "Characterizing autism spectrum disorders by key biochemical pathways", Front Neurosci, 9, pp.313~ (2015)
- Hutsler JJ, "Increased dendritic spine densities on cortical projection neurons in autism spectrum disorders", Brain Res, 1309, pp.83~94 (2010)
- Horgusluoglu E, "Adult neurogenesis and neurodegenerative diseases : A systems biology perspective", Am J Med Genet B Neuropsychiatr Genet, 174, pp.93~112 (2017)
- Betizeau M, "From stem cells to comparative corticogenesis: a bridge too far?", Stem cell Investing, 3, pp.39~ (2016)
- Osborne LR, "Caveat mTOR : aberrant signaling disrupts corticogenesis", J Clin Invest, 120, pp.1392~1395 (2010)
- Gatto CL, "Genetic controls balancing excitatory and inhibitory synaptogenesis in neurodevelopmental disorder models", Front Synaptic Neurosci, 2, pp.4~ (2010)
- Zatkova M, "Synapse alterations in autism : Review of animal model findings", Biomed Pap Med Fac Uni Palacky Olomouc Czech Repub, 160, pp.201~210 (2016)
- Ishii K, "Reelin and neuropsychiatric disorders", Frontiers Cell Neurosci, 10, pp.229~ (2016)
- Oblak AL, "Decreased GABAB receptors in the cingulate cortex and fusiform gyrus in autism", J Neurochem, 114, pp.1414~1423 (2010)
- Notwell JH, "TBR1regulates autism risk genes in the developing neocortex", Genome Res, 26, pp.1013~1022 (2016)
- Hanashima C, "Switching modes in corticogenesis : mechanisms of neuronal subtype transitions and integration in the cerebral cortex", Front Neurosci, 9, pp.274~ (2015)
- Ichtchenko K, "Neuroligin 1:a splice site-specific ligand for β-neurexins", Cell, 81, pp.435~443 (1995)
- Chen J, "Synaptic proteins and receptors defects in autism spectrum disorders", Front Cell Neurosci, 8, pp.276~ (2014)
- Williams E, "Above genetics : lessons from cerebral development in autism", Transl Neurosci, 2, pp.106~120 (2011)
- Wisniewska MB, "Physiological role of β-catenin", TCF signaling in neurons of the adult brain, 2013, pp.38, 1144~1155
- Feliciano DM, "Single-cell Tsc1 knockout during corticogenesis generates tuber-like lesions and reduces seizure threshold in mice", J Clin Invest, 121, pp.1596~1607 (2011)
- Won H, "Autism spectrum disorder causes, mechanisms, and treatments : focus on neuronal synapses", Front Molecu Neurosci, 6, pp.19~ (2013)
- Lahiri DK, "Autism as early neurodevelopmental disorder : evidence for an sAPP-mediated anabolic pathway", Front Cell Neuro, 7, pp.94~ (2013)
- Lin TV, "Normalizing translation through 4E-BP prevents mTOR-driven cortical mislamination and ameliorates aberrant neuron integration", Proc Natl Acad Sci U S A, 113, pp.11330~11335 (2016)
- Oron O, "Delineating the Common Biological Pathways Perturbed by ASD’s Genetic Etiology : Lessons from Network-Based Studies", Int J Molecu Sci, 18, pp.828~ (2017)
- Noelanders R, "How Wnt signaling builds the brain : bridging development and disease", Neuroscientist, 23, pp.314~329 (2017)
- Jung NH, "Impaired induction of long‐term potentiation‐like plasticity in patients with high‐functioning autism and Asperger syndrome", Dev Med Child Neurol, 55, pp.83~89 (2013)
- Wen Y, "Pathway network analyses for autism reveal multisystem involvement, major overlaps with other diseases and convergence upon MAPK and calcium signaling", PLoS One, 11, pp.e0153329~ (2016)
- O'Loghlen A, "N-acetyl-cysteine abolishes hydrogen peroxideinduced modification of eukaryotic initiation factor 4F activity via distinct signalling pathways", Cell Signal, 18, pp.21~31 (2006)
- Laplante M, "mTOR signaling at a glance", J Cell Sci, 122, pp.3589~3594 (2009)
- Murugan AK, "Mutations in critical domains confer the human mTOR gene strong tumorigenicity", J Bio Chem, 288, pp.6511~6521 (2013)
- Conciatori F, "mTOR cross-talk in cancer and potential for combination therapy", Cancers, 10, pp.23~ (2018)
- Audet-Walsh É, "Nuclear mTOR acts as a transcriptional integrator of the androgen signaling pathway in prostate cancer", Genes Dev, 31, pp.1228~1242 (2017)
- Xu J, "Mechanistically distinct cancer-associated mTOR activation clusters predict sensitivity to rapamycin", J Clin Invest, 126, pp.3526~3540 (2016)
- Davis NM, "Deregulation of the EGFR", PI3K, Akt, pp.mTORC1pathway in breast cancer : possibilities for therapeutic intervention, Oncotarget[DOI]
- Samidurai A, "Emerging Role of mTOR Signaling-Related miRNAs in Cardiovascular Diseases", Oxid Med Cell Longev, 2018, pp.23~ (2018)
- Viana SD, "Therapeutic Use of mTOR Inhibitors in Renal Diseases : Advances, Drawbacks, and Challenges", Oxid Med Cell Longev, 2018, pp.3693625~ (2018)
- Lawrence J, "The role of the mammalian target of rapamycin(mTOR)in pulmonary fibrosis", Inter J Mol Sci, 19, pp.778~ (2018)
- Chau GC, "mTOR controls ChREBP transcriptional activity and pancreatic β cell survival under diabetic stress", J Cell Biol, 216, pp.2091~2105 (2017)
- Striano P, "Genetics : mutations in mTOR pathway linked to megalencephaly syndromes", Nat Rev Neurol, 8(10), pp.542~ (2012)
- Mirzaa GM, "Association of MTOR mutations with developmental brain disorders, including megalencephaly, focal cortical dysplasia, and pigmentary mosaicism", JAMA Neurol, 73, pp.836~845 (2016)
- Lee JH, "De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly", Nat Genet, 44, pp.941~ (2012)
- Panner A, "mTOR controls FLIPS translation and TRAIL sensitivity in glioblastoma multiforme cells", Mol Cell Biol, 25, pp.8809~8823 (2005)
- Lim JS, "Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy", Nat Med, 21(4), pp.395~ (2015)
- Ryskalin L, "mTOR-dependent cell proliferation in the brain", Biomed Res Int, 2017, pp.14~ (2017)
- Costa-Mattioli M, "mTOR complexes in neurodevelopmental and neuropsychiatric disorders", Nat Neurosci, 16, pp.1537~1543 (2013)
- Lee HK, "mTORC2(Rictor)in Alzheimer’s disease and reversal of amyloid-expression-induced insulin resistance and toxicity in rat primary cortical neurons", J Alz Dis, 56, pp.1015~1036 (2017)
- Dan HC, "Akt-dependent activation of mTORC1 Involves phosphorylation of mTOR by IKKalpha", J Bio Chem, 289, pp.25227~25240 (2014)
- Takei N, "mTOR signaling and its roles in normal and abnormal brain development", Front Mol Neuro, 7, pp.28~ (2014)
- Winden KD, "Abnormal mTOR activation in autism", Annu Rev of Neuro, 41, pp.1~23 (2018)
- Muranen T, "Inhibition of PI3K", mTOR leads to adaptive resistance in matrixattached cancer cells, 2012, pp.21, 227~239
- Sawicka K, "Dysregulation of mTOR signaling in neuropsychiatric disorders : therapeutic implications", Neuropsychopharma, 37, pp.305~ (2012)
- Sharma A, "Dysregulation of mTOR signaling in fragile X syndrome", J Neurosci, 30, pp.694~702 (2010)
- Sun J, "Imbalanced mechanistic target of rapamycin C1 and C2 activity in the cerebellum of Angelman syndrome mice impairs motor function", J Neurosci, 35, pp.4706~4718 (2015)
- Piven J, "Toward a conceptual framework for early brain and behavior development in autism", Mol psych, 22, pp.1385~ (2017)
- Lipton JO, "The neurology of mTOR", Neuron, 84, pp.275~291 (2014)
- Nicolini C, "The valproic acid-induced rodent model of autism", Exper Neuro, 299, pp.217~227 (2018)
- Liu X, "Idiopathic autism : cellular and molecular phenotypes in pluripotent stem cell-derived neurons", Mol Neurobiol, 54, pp.4507~4523 (2017)
- Meyza KZ, "The BTBR mouse model of idiopathic autism-Current view on mechanisms", Neurosci Biobehav Rev, 76, pp.99~110 (2017)
- Onore C, "Dynamic Akt", mTOR signaling in children with autism spectrum disorder, 2017, pp.5, 43~
- De Rosa BA, "Convergent Pathways in Idiopathic Autism Revealed by Time Course Transcriptomic Analysis of Patient-Derived Neurons", Scienti Rep, 8, pp.8423~ (2018)
- Showkat M, "mTOR signaling in protein translation regulation : implications in cancer genesis and therapeutic interventions", Mol Biol Int, 2014, pp.14~ (2014)
- Kelleher III RJ, "The autistic neuron:troubled translation?", Cell, 135, pp.401~406 (2008)
- Dowling RJ, "mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs", Science, 328, pp.1172~1176 (2010)
- Kanne SM, "The role of adaptive behavior in autism spectrum disorders : Implications for functional outcome", J Autism Dev Disord, 41, pp.1007~1018 (2011)
- Jossé L, "mTORC1signalling and eIF4E", 4E-BP1 translation initiation factor stoichiometry influence recombinant protein productivity from GS-CHOK1 cells, 2016, pp.473, 4651~4664
- Jernigan CS, "The mTOR signaling pathway in the prefrontal cortex is compromised in major depressive disorder", Prog Neuro-Psychopharmacol Biol Psychiatry, 35, pp.1774~1779 (2011)
- Xiao Z, "Programming for CD8 T cell memory development requires IL-12 or type I IFN", J Immunol, 182, pp.2786~2794 (2009)
- Shott RH, "Development of kinomic analyses to identify dysregulated signaling pathways in cells expressing cytoplasmic PrP", Virol J, 11, pp.175~ (2014)
- Cao R, "Translational control of entrainment and synchrony of the suprachiasmatic circadian clock by mTOR", 4E-BP1 signaling, 2013, pp.79, 712~724
- Gkogkas CG, "Autismrelated deficits via dysregulated eIF4E-dependent translational control", Nature, 493, pp.371~ (2013)
- Dennis MD, "Mechanistic target of rapamycin complex 1(mTORC1)-mediated phosphorylation is governed by competition between substrates for interaction with raptor", J Bio Chem, 288, pp.10~19 (2013)
- Zhao XF, "Phospho-p70S6K and cdc2", cdk1 as therapeutic targets for diffuse large B-cell lymphoma, 2009, pp.13, 1085~1093
- Bahrami BF, "p70 Ribosomal protein S6 kinase(Rps6kb1) : an update", J Clin Pathol, 12, pp.1019~1025 (2014)
- Bahrami F, "Monepantel induces autophagy in human ovarian cancer cells through disruption of the mTOR", p70S6K signalling pathway, 2014, pp.4, 558~571
- Biever A, "Ribosomal protein S6 phosphorylation in the nervous system : from regulation to function", Front Mol Neuro, 8, pp.75~ (2015)
- Kwon CH, "Pten regulates neuronal arborization and social interaction in mice", Neuron, 50, pp.377~388 (2006)
- Ogawa S, "A seizure-prone phenotype is associated with altered free-running rhythm in Pten mutant mice", Brain Res, 1168, pp.112~123 (2007)
- Lafourcade CA, "Rheb activation in subventricular zone progenitors leads to heterotopia, ectopic neuronal differentiation, and rapamycin-sensitive olfactory micronodules and dendrite hypertrophy of newborn neurons", J Neurosci, 33, pp.2419~2431 (2013)
- Tavazoie SF, "Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2", Nat Neurosci, 8, pp.1727~ (2005)
- Thomanetz V, "Ablation of the mTORC2 component rictor in brain or Purkinje cells affects size and neuron morphology", J Cell Biol, 201, pp.293~308 (2013)
- Weston MC, "Loss of mTOR repressors Tsc1 or Pten has divergent effects on excitatory and inhibitory synaptic transmission in single hippocampal neuron cultures", Front Mol Neurosci, 7, pp.1~ (2014)
- Choi YJ, "Tuberous sclerosis complex proteins control axon formation", Genes Dev, 22, pp.2485~2495 (2008)
