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Psychotropic Medications and the Treatment of Human Prion Diseases

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Prion diseases are rare, rapidly progressive, fatal neurodegenerative illnesses caused by an abnormal isoform of the native prion protein. Creutzfeldt-Jakob disease (CJD) is the most prevalent human prion disease with three possible etiologies: sporadic, genetic, and acquired. Although acquired forms of prion disease have received the most attention, most cases are sporadic or genetic and are thus unpreventable. There is some literature on neurotransmitter system dysregulation in animal and human models of prion diseases. Several studies indicate that there is a disproportional amount of serotonin dysregulation in prion diseases and that prion-mediated cytotoxicity may be blocked by N-methyl Daspartate (NMDA) receptor antagonists. Prion disease therapeutic investigations have mainly consisted of basic science research, which has elucidated the importance of molecular structure in preventing prion protein conversion. Typical neuroleptics and tricyclic antidepressants have been the primary psychotropic medications studied in humans due to their heterocyclic structures. Recent studies have correlated lipid disruption to these structurally similar compounds with antiprion activity. Preliminary studies suggest that lithium mediated inhibition of glycogen synthetase kinase 3 and lithium-induced autophagy may be avenues for further research. Many studies require replication in other experimental settings. Thus far, treatment strategies have focused on aborting prion protein conversion and as such have limited therapeutic usefulness given the rapidity of disease progression and difficulty in establishing ante-mortem diagnoses of prion diseases. There is a paucity of research examining the prevention of prion diseases in at risk populations (i.e. genetic and acquired prion diseases).

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Keywords: Creutzfeldt-Jakob disease; Prion disease; antidepressants; antipsychotics; neurotransmitters; pharmacology; prion; treatment

Document Type: Research Article

Publication date: 2009-11-01

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  • CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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