Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder

article Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder published yes Dora-Clara Tarlungeanu author 2ABCE612-F248-11E8-B48F-1D18A9856A87 Elena Deliu author 37A40D7E-F248-11E8-B48F-1D18A9856A870000-0002-7370-5293 Christoph Dotter author 4C66542E-F248-11E8-B48F-1D18A9856A870000-0002-9033-9096 Majdi Kara author Philipp Janiesch author Mariafrancesca Scalise author Michele Galluccio author Mateja Tesulov author Emanuela Morelli author 3F4D1282-F248-11E8-B48F-1D18A9856A87 Fatma Sönmez author Kaya Bilgüvar author Ryuichi Ohgaki author Yoshikatsu Kanai author Anide Johansen author Seham Esharif author Tawfeg Ben Omran author Meral Topcu author Avner Schlessinger author Cesare Indiveri author Kent Duncan author Ahmet Caglayan author Murat Günel author Joseph Gleeson author Gaia Novarino author 3E57A680-F248-11E8-B48F-1D18A9856A870000-0002-7673-7178 GaNo department Transmembrane Transporters in Health and Disease project Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. We previously described abnormalities in the branched-chain amino acid (BCAA) catabolic pathway as a cause of ASD. Here, we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation, and severe neurological abnormalities. Furthermore, we identified several patients with autistic traits and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. Finally, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for the BCAA in human brain function. https://research-explorer.ista.ac.at/download/1183/5030/IST-2017-771-v1+1_Tarlungeanu_et_al._Final_edited.pdf application/pdfno Cell Press2016 eng Cell 00038947050001210.1016/j.cell.2016.11.013 16761481 - 1494 https://research-explorer.ista.ac.at/record/395 Tarlungeanu, Dora-Clara, Elena Deliu, Christoph Dotter, Majdi Kara, Philipp Janiesch, Mariafrancesca Scalise, Michele Galluccio, et al. “Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.” Cell. Cell Press, 2016. <a href="https://doi.org/10.1016/j.cell.2016.11.013">https://doi.org/10.1016/j.cell.2016.11.013</a>. D.-C. Tarlungeanu et al., “Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder,” Cell, vol. 167, no. 6. Cell Press, pp. 1481–1494, 2016. Tarlungeanu D-C, Deliu E, Dotter C, et al. Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell. 2016;167(6):1481-1494. doi:<a href="https://doi.org/10.1016/j.cell.2016.11.013">10.1016/j.cell.2016.11.013</a> D.-C. Tarlungeanu, E. Deliu, C. Dotter, M. Kara, P. Janiesch, M. Scalise, M. Galluccio, M. Tesulov, E. Morelli, F. Sönmez, K. Bilgüvar, R. Ohgaki, Y. Kanai, A. Johansen, S. Esharif, T. Ben Omran, M. Topcu, A. Schlessinger, C. Indiveri, K. Duncan, A. Caglayan, M. Günel, J. Gleeson, G. Novarino, Cell 167 (2016) 1481–1494. Tarlungeanu, D.-C., Deliu, E., Dotter, C., Kara, M., Janiesch, P., Scalise, M., … Novarino, G. (2016). Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell. Cell Press. <a href="https://doi.org/10.1016/j.cell.2016.11.013">https://doi.org/10.1016/j.cell.2016.11.013</a> Tarlungeanu D-C, Deliu E, Dotter C, Kara M, Janiesch P, Scalise M, Galluccio M, Tesulov M, Morelli E, Sönmez F, Bilgüvar K, Ohgaki R, Kanai Y, Johansen A, Esharif S, Ben Omran T, Topcu M, Schlessinger A, Indiveri C, Duncan K, Caglayan A, Günel M, Gleeson J, Novarino G. 2016. Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell. 167(6), 1481–1494. Tarlungeanu, Dora-Clara, et al. “Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.” Cell, vol. 167, no. 6, Cell Press, 2016, pp. 1481–94, doi:<a href="https://doi.org/10.1016/j.cell.2016.11.013">10.1016/j.cell.2016.11.013</a>. 11832018-12-11T11:50:35Z2026-07-22T22:30:41Z