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Hayashi-Takagi A, Araki Y, Nakamura M, Vollrath B, Duron SG, Yan Z, Kasai H, Huganir RL, Campbell DA, Sawa A. PAKs inhibitors ameliorate schizophrenia-associated dendritic spine deterioration in vitro and in vivo during late adolescence. Proc Natl Acad Sci U S A . 2014 Apr 29 ; 111(17):6461-6. PubMed Abstract

Comments on Paper and Primary News
Comment by:  Albert H. C. Wong
Submitted 16 April 2014 Posted 16 April 2014

These are very interesting and novel results using knowledge of DISC1 and dendritic spine biology to test new drugs targeting a pathway implicated in schizophrenia. It is encouraging to see successful, mechanism-based approaches to discover new therapeutic interventions for schizophrenia. Although there is a long road to clinical translation, efforts such as these offer hope that drugs with new targets will emerge. The preventative potential of the PAK inhibitors is also very important, since all current treatments are symptomatic and do not change the course of illness.

View all comments by Albert H. C. Wong

Comment by:  Amy Ramsey
Submitted 23 April 2014 Posted 23 April 2014

New Research Identifies PAK1 as a Promising Target for Schizophrenia Treatment
Schizophrenia has been described as a disease of the synapse, in part because postmortem brain studies have uncovered a loss of dendritic spines, the physical structures of glutamate synapses (Glantz and Lewis, 2000; Sweet et al., 2009; Garey et al., 1998). Interestingly, the same deficits in dendritic spines are seen in a number of pharmacological and genetic animal models of the disorder (Lee et al., 2011; Ramsey et al., 2011; Elsworth et al., 2011; Chen et al., 2008). Despite these intriguing observations, it has been difficult to move beyond correlations to show that spine deficits cause schizophrenia symptoms, and that reversing these deficits will reverse...  Read more

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