Decoding the contribution of dopaminergic genes and pathways to autism spectrum disorder (ASD). / Nguyen, Michael; Roth, Andrew; Kyzar, Evan J.; Poudel, Manoj K.; Wong, Keith; Stewart, Adam Michael; Kalueff, Allan V.
In: Neurochemistry International, Vol. 66, No. 1, 01.2014, p. 15-26.Research output: Contribution to journal › Review article › peer-review
}
TY - JOUR
T1 - Decoding the contribution of dopaminergic genes and pathways to autism spectrum disorder (ASD)
AU - Nguyen, Michael
AU - Roth, Andrew
AU - Kyzar, Evan J.
AU - Poudel, Manoj K.
AU - Wong, Keith
AU - Stewart, Adam Michael
AU - Kalueff, Allan V.
PY - 2014/1
Y1 - 2014/1
N2 - Autism spectrum disorder (ASD) is a debilitating brain illness causing social deficits, delayed development and repetitive behaviors. ASD is a heritable neurodevelopmental disorder with poorly understood and complex etiology. The central dopaminergic system is strongly implicated in ASD pathogenesis. Genes encoding various elements of this system (including dopamine receptors, the dopamine transporter or enzymes of synthesis and catabolism) have been linked to ASD. Here, we comprehensively evaluate known molecular interactors of dopaminergic genes, and identify their potential molecular partners within up/down-steam signaling pathways associated with dopamine. These in silico analyses allowed us to construct a map of molecular pathways, regulated by dopamine and involved in ASD. Clustering these pathways reveals groups of genes associated with dopamine metabolism, encoding proteins that control dopamine neurotransmission, cytoskeletal processes, synaptic release, Ca2+ signaling, as well as the adenosine, glutamatergic and gamma-aminobutyric systems. Overall, our analyses emphasize the important role of the dopaminergic system in ASD, and implicate several cellular signaling processes in its pathogenesis.
AB - Autism spectrum disorder (ASD) is a debilitating brain illness causing social deficits, delayed development and repetitive behaviors. ASD is a heritable neurodevelopmental disorder with poorly understood and complex etiology. The central dopaminergic system is strongly implicated in ASD pathogenesis. Genes encoding various elements of this system (including dopamine receptors, the dopamine transporter or enzymes of synthesis and catabolism) have been linked to ASD. Here, we comprehensively evaluate known molecular interactors of dopaminergic genes, and identify their potential molecular partners within up/down-steam signaling pathways associated with dopamine. These in silico analyses allowed us to construct a map of molecular pathways, regulated by dopamine and involved in ASD. Clustering these pathways reveals groups of genes associated with dopamine metabolism, encoding proteins that control dopamine neurotransmission, cytoskeletal processes, synaptic release, Ca2+ signaling, as well as the adenosine, glutamatergic and gamma-aminobutyric systems. Overall, our analyses emphasize the important role of the dopaminergic system in ASD, and implicate several cellular signaling processes in its pathogenesis.
KW - Autism
KW - Dopaminergic system
KW - Genetics
KW - Molecular pathways
KW - Translational research
UR - http://www.scopus.com/inward/record.url?scp=84893182133&partnerID=8YFLogxK
U2 - 10.1016/j.neuint.2014.01.002
DO - 10.1016/j.neuint.2014.01.002
M3 - Review article
C2 - 24412511
AN - SCOPUS:84893182133
VL - 66
SP - 15
EP - 26
JO - Neurochemistry International
JF - Neurochemistry International
SN - 0197-0186
IS - 1
ER -
ID: 9440819