PAKs inhibitors ameliorate schizophrenia-associated dendritic spine deterioration in vitro and in vivo during late adolescence
Copyright policy )PAKs inhibitors ameliorate schizophrenia-associated dendritic spine deterioration in vitro and in vivo during late adolescence
Significance 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 involved in its pathophysiology. In this study, we studied a biological pathway underlying synaptic disturbance and examined whether p21-activated kinase inhibitors ameliorate the pathology in vitro and in vivo. The beneficial effects of these inhibitors reported here may provide us with an opportunity for drug discovery in major mental illnesses with synaptic disturbance.
- Johns Hopkins Medicine United States
- Japan Science and Technology Agency Japan
- State University of New York United States
- State University of New York at Potsdam United States
- University of Tokyo Japan
Aging, Neuronal Plasticity, Behavior, Animal, Pyridones, Dendritic Spines, Prefrontal Cortex, Nerve Tissue Proteins, Receptors, N-Methyl-D-Aspartate, Rats, Disease Models, Animal, Mice, Pyrimidines, p21-Activated Kinases, Gene Knockdown Techniques, Synapses, Schizophrenia, Animals, RNA Interference, Protein Kinase Inhibitors
Aging, Neuronal Plasticity, Behavior, Animal, Pyridones, Dendritic Spines, Prefrontal Cortex, Nerve Tissue Proteins, Receptors, N-Methyl-D-Aspartate, Rats, Disease Models, Animal, Mice, Pyrimidines, p21-Activated Kinases, Gene Knockdown Techniques, Synapses, Schizophrenia, Animals, RNA Interference, Protein Kinase Inhibitors
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