TY - JOUR
T1 - Genetic findings in obsessive-compulsive disorder connect to brain-derived neutrophic factor and mammalian target of rapamycin pathways
T2 - Implications for drug development
AU - Grados, Marco
AU - Sung, Hyung Mo
AU - Kim, Sejin
AU - Srivastava, Siddharth
N1 - Publisher Copyright:
© 2014 Wiley Periodicals, Inc.
PY - 2014/9
Y1 - 2014/9
N2 - Preclinical Research Traditional pharmacological approaches to the treatment of obsessive-compulsive disorder (OCD) are based on affecting serotonergic and dopaminergic transmission in the central nervous system. However, genetic epidemiology findings are pointing to glutamate pathways and developmental genes as etiological in OCD. A review of recent genetic findings in OCD is conducted, and bioinformatics approaches are used to locate pathways relevant to neuroprotection. The OCD susceptibility genes DLGAP1, RYR3, PBX1-MEIS2, LMX1A and candidate genes BDNF and GRIN2B are components of the neuronal growth, differentiation and neurogenesis pathways BDNF-mTOR. These pathways are emerging as a promising area of research for the development of neuroprotective pharmaceuticals. Emergent genetic epidemiologic data on OCD and repetitive behaviors may support new approaches for pharmacological discovery. Neuroprotective approaches that take into consideration glutamate-mediated BDNF-mTOR pathways are suggested by OCD susceptibility genes.
AB - Preclinical Research Traditional pharmacological approaches to the treatment of obsessive-compulsive disorder (OCD) are based on affecting serotonergic and dopaminergic transmission in the central nervous system. However, genetic epidemiology findings are pointing to glutamate pathways and developmental genes as etiological in OCD. A review of recent genetic findings in OCD is conducted, and bioinformatics approaches are used to locate pathways relevant to neuroprotection. The OCD susceptibility genes DLGAP1, RYR3, PBX1-MEIS2, LMX1A and candidate genes BDNF and GRIN2B are components of the neuronal growth, differentiation and neurogenesis pathways BDNF-mTOR. These pathways are emerging as a promising area of research for the development of neuroprotective pharmaceuticals. Emergent genetic epidemiologic data on OCD and repetitive behaviors may support new approaches for pharmacological discovery. Neuroprotective approaches that take into consideration glutamate-mediated BDNF-mTOR pathways are suggested by OCD susceptibility genes.
KW - FKBP12
KW - GRM5
KW - brain-derived neutrophic factor (BDNF)
KW - mammalian target of rapamycin (mTOR)
KW - obsessive-compulsive disorder (OCD)
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U2 - 10.1002/ddr.21223
DO - 10.1002/ddr.21223
M3 - Review article
C2 - 25195581
AN - SCOPUS:84925598644
SN - 0272-4391
VL - 75
SP - 372
EP - 383
JO - Drug Development Research
JF - Drug Development Research
IS - 6
ER -