Molecular mechanisms for targeted ASD treatments

被引:26
作者
Basilico, Bernadette [1 ]
Morandell, Jasmin [1 ]
Novarino, Gaia [1 ]
机构
[1] IST Austria, Klosterneuburg, Austria
基金
奥地利科学基金会;
关键词
FRAGILE-X-SYNDROME; MOUSE MODEL; SYNAPTIC PLASTICITY; NEURONAL MIGRATION; TRANSCRIPTIONAL REGULATION; PROTEIN-SYNTHESIS; ANGELMAN SYNDROME; SOCIAL DEFICITS; CRITICAL-PERIOD; RISK GENES;
D O I
10.1016/j.gde.2020.06.004
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The possibility to generate construct valid animal models enabled the development and testing of therapeutic strategies targeting the core features of autism spectrum disorders (ASDs). At the same time, these studies highlighted the necessity of identifying sensitive developmental time windows for successful therapeutic interventions. Animal and human studies also uncovered the possibility to stratify the variety of ASDs in molecularly distinct subgroups, potentially facilitating effective treatment design. Here, we focus on the molecular pathways emerging as commonly affected by mutations in diverse ASD-risk genes, on their role during critical windows of brain development and the potential treatments targeting these biological processes.
引用
收藏
页码:126 / 137
页数:12
相关论文
共 159 条
[91]   Chronic Pharmacological mGlu5 Inhibition Corrects Fragile X in Adult Mice [J].
Michalon, Aubin ;
Sidorov, Michael ;
Ballard, Theresa M. ;
Ozmen, Laurence ;
Spooren, Will ;
Wettstein, Joseph G. ;
Jaeschke, Georg ;
Bear, Mark F. ;
Lindemann, Lothar .
NEURON, 2012, 74 (01) :49-56
[92]  
Morandell J, 2020, BIORXIV, DOI [10.1101/2020.01.10.902064, DOI 10.1101/2020.01.10.902064]
[93]   Disruption of hippocampus-regulated behavioural and cognitive processes by heterozygous constitutive deletion of SynGAP [J].
Muhia, Mary ;
Yee, Benjamin K. ;
Feldon, Joram ;
Markopoulos, Foivos ;
Knuesel, Irene .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2010, 31 (03) :529-543
[94]   No Evidence for Association of Autism with Rare Heterozygous Point Mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contactin-Associated Proteins or Contactins [J].
Murdoch, John D. ;
Gupta, Abha R. ;
Sanders, Stephan J. ;
Walker, Michael F. ;
Keaney, John ;
Fernandez, Thomas V. ;
Murtha, Michael T. ;
Anyanwu, Samuel ;
Ober, Gordon T. ;
Raubeson, Melanie J. ;
DiLullo, Nicholas M. ;
Villa, Natalie ;
Waqar, Zainabdul ;
Sullivan, Catherine ;
Gonzalez, Luis ;
Willsey, A. Jeremy ;
Choe, So-Yeon ;
Neale, Benjamin M. ;
Daly, Mark J. ;
State, Matthew W. .
PLOS GENETICS, 2015, 11 (01)
[95]   MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin [J].
Nan, XS ;
Campoy, FJ ;
Bird, A .
CELL, 1997, 88 (04) :471-481
[96]   PTEN depletion rescues axonal growth defect and improves survival in SMN-deficient motor neurons [J].
Ning, Ke ;
Drepper, Carsten ;
Valori, Chiara F. ;
Ahsan, Mansoor ;
Wyles, Matthew ;
Higginbottom, Adrian ;
Herrmann, Thomas ;
Shaw, Pamela ;
Azzouz, Mimoun ;
Sendtner, Michael .
HUMAN MOLECULAR GENETICS, 2010, 19 (16) :3159-3168
[97]   Reelin promotes hippocampal dendrite development through the VLDLR/ApoER2-Dab1 pathway [J].
Niu, S ;
Renfro, A ;
Quattrocchi, CC ;
Sheldon, M ;
D'Arcangelo, G .
NEURON, 2004, 41 (01) :71-84
[98]   The Reelin Signaling Pathway Promotes Dendritic Spine Development in Hippocampal Neurons [J].
Niu, Sanyong ;
Yabut, Odessa ;
D'Arcangelo, Gabriella .
JOURNAL OF NEUROSCIENCE, 2008, 28 (41) :10339-10348
[99]   TBR1 regulates autism risk genes in the developing neocortex [J].
Notwell, James H. ;
Heavner, Whitney E. ;
Darbandi, Siavash Fazel ;
Katzman, Sol ;
McKenna, William L. ;
Ortiz-Londono, Christian F. ;
Tastad, David ;
Eckler, Matthew J. ;
Rubenstein, John L. R. ;
McConnell, Susan K. ;
Chen, Bin ;
Bejerano, Gill .
GENOME RESEARCH, 2016, 26 (08) :1013-1022
[100]   Mutations in BCKD-kinase Lead to a Potentially Treatable Form of Autism with Epilepsy [J].
Novarino, Gaia ;
El-Fishawy, Paul ;
Kayserili, Hulya ;
Meguid, Nagwa A. ;
Scott, Eric M. ;
Schroth, Jana ;
Silhavy, Jennifer L. ;
Kara, Majdi ;
Khalil, Rehab O. ;
Ben-Omran, Tawfeg ;
Ercan-Sencicek, A. Gulhan ;
Hashish, Adel F. ;
Sanders, Stephan J. ;
Gupta, Abha R. ;
Hashem, Hebatalla S. ;
Matern, Dietrich ;
Gabriel, Stacey ;
Sweetman, Larry ;
Rahimi, Yasmeen ;
Harris, Robert A. ;
State, Matthew W. ;
Gleeson, Joseph G. .
SCIENCE, 2012, 338 (6105) :394-397