2025
Dysregulation of mTOR signalling is a converging mechanism in lissencephaly
Zhang C, Liang D, Ercan-Sencicek A, Bulut A, Cortes J, Cheng I, Henegariu O, Nishimura S, Wang X, Peksen A, Takeo Y, Caglar C, Lam T, Koroglu M, Narayanan A, Lopez-Giraldez F, Miyagishima D, Mishra-Gorur K, Barak T, Yasuno K, Erson-Omay E, Yalcinkaya C, Wang G, Mane S, Kaymakcalan H, Guzel A, Caglayan A, Tuysuz B, Sestan N, Gunel M, Louvi A, Bilguvar K. Dysregulation of mTOR signalling is a converging mechanism in lissencephaly. Nature 2025, 1-10. PMID: 39743596, DOI: 10.1038/s41586-024-08341-9.Peer-Reviewed Original ResearchP53-induced death domain protein 1Miller-Dieker lissencephaly syndromeMolecular mechanismsDysregulation of protein translationDysregulation of mTOR signalingDomain protein 1Activity of mTOR complexesMTOR pathwayRelevant molecular mechanismsProtein translationHuman lissencephalyClinically relevant molecular mechanismsRecessive mutationsRare mutationsMiller-DiekerGene expressionCerebral cortex developmentMTOR complexesSpectrum disorderMolecular defectsMTOR signalingCongenital brain malformationsProtein 1GeneticsAssociated with epilepsy
2016
Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder
Tărlungeanu DC, Deliu E, Dotter CP, Kara M, Janiesch PC, Scalise M, Galluccio M, Tesulov M, Morelli E, Sonmez FM, Bilguvar K, Ohgaki R, Kanai Y, Johansen A, Esharif S, Ben-Omran T, Topcu M, Schlessinger A, Indiveri C, Duncan KE, Caglayan AO, Gunel M, Gleeson JG, Novarino G. Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder. Cell 2016, 167: 1481-1494.e18. PMID: 27912058, PMCID: PMC5554935, DOI: 10.1016/j.cell.2016.11.013.Peer-Reviewed Original ResearchConceptsBlood-brain barrierBrain barrierBrain amino acid profilesLarge neutral amino acid transporterAutism spectrum disorderAdult mutant miceBranched-chain amino acid (BCAA) catabolic pathwaySevere neurological abnormalitiesNeutral amino acid transporterIntracerebroventricular administrationNeurological syndromeNeurological abnormalitiesNeurological conditionsSpectrum disorderSLC7A5 geneMotor delayAmino acid transportAmino acid transportersMutant miceNormal levelsBrain functionHuman brain functionEndothelial cellsHomozygous mutationCauses of ASD