Psychotropics regulate Skp1a, Aldh1a1, and Hspa8 transcription--potential to delay Parkinson's disease

Recently, the genes p19 S-phase kinase-associated protein 1A (SKP1), huntingtin interacting protein-2 (UBE2K), aldehyde dehydrogenase family 1 subfamily A1 (ALDH1A1), 19 S proteasomal protein PSMC4, and heat shock 70-kDa protein 8 (HSPA8) have been found to predict the onset and progression of Parkinson's disease (PD). These findings prompted a review of the effects of commonly prescribed psychiatric medicines, drugs that are used in treating PD, on the expression of these genes. Findings in the published medical literature were reviewed and gene expression data in the Gene Expression Omnibus Profiles database were analyzed. The results indicate that fluoxetine upregulated the risk-attenuating genes Skp1a and Aldh1a1 and olanzapine downregulated risk-enhancing Hspa8 while also downregulating Aldh1a1. Less conclusive evidence suggested that fluoxetine might also downregulate Hspa8 and clozapine might downregulate risk-enhancing Ube2k, but that olanzapine might upregulate Ube2k. Together, the present findings suggest that these psychotropics may delay PD onset (fluoxetine, olanzapine, and perhaps clozapine) and progression (fluoxetine, clozapine, and perhaps olanzapine). These gene expression findings should be replicated by RT-PCR studies in humans and, if confirmed, these drugs should then be studied in animal models and PD patients.