PAKs inhibitors ameliorate schizophrenia-associated dendritic spine deterioration in vitro and in vivo during late adolescence

Drug discovery in psychiatry has been limited to chemical modifications of compounds originally discovered serendipitously. Therefore, more mechanism-oriented strategies of drug discovery for mental disorders are awaited. Schizophrenia is a devastating mental disorder with synaptic disconnectivity i...

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Veröffentlicht in:	Proceedings of the National Academy of Sciences - PNAS 2014-04, Vol.111 (17), p.6461-6466
Hauptverfasser:	Hayashi-Takagi, Akiko, Araki, Yoichi, Nakamura, Mayumi, Vollrath, Benedikt, Duron, Sergio G., Yan, Zhen, Kasai, Haruo, Huganir, Richard L., Campbell, David A., Sawa, Akira
Format:	Artikel
Sprache:	eng
Schlagworte:	Adolescence Adolescents adulthood Aging - pathology animal models Animals Behavior, Animal - drug effects Biological Sciences cerebral cortex Dendritic spines Dendritic Spines - drug effects Dendritic Spines - enzymology Dendritic Spines - pathology Disease Models, Animal Dosage Drug discovery drugs Gene expression Gene Knockdown Techniques Genotype & phenotype glutamic acid image analysis Imaging Inhibitors Mental disorders Mental illness Mice Nerve Tissue Proteins - metabolism Neuronal Plasticity - drug effects Neurons Neuropsychology p21-Activated Kinases - antagonists & inhibitors p21-Activated Kinases - metabolism Pathology pathophysiology patients phosphotransferases (kinases) Prefrontal Cortex - drug effects Prefrontal Cortex - pathology Prefrontal Cortex - physiopathology Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacology Protein Kinase Inhibitors - therapeutic use Psychiatry Psychopharmacology Pyridones - chemistry Pyridones - pharmacology Pyridones - therapeutic use Pyrimidines - chemistry Pyrimidines - pharmacology Pyrimidines - therapeutic use R&D Rats Receptors, N-Methyl-D-Aspartate - metabolism Research & development RNA Interference - drug effects Schizophrenia Schizophrenia - drug therapy Schizophrenia - enzymology Schizophrenia - physiopathology Spine Synapses Synapses - drug effects Synapses - metabolism
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