Convergent mechanisms in etiologically-diverse dystonias

• Type of Material: Article
• Authors: Valerie B. Thompson, Emory University; Hyder A Jinnah, Emory University; Ellen Hess, Emory University
• Language: English
• Date: 2011-12
• Publisher: Taylor & Francis: STM, Behavioural Science and Public Health Titles - No Open Select
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 Informa UK, Ltd.
• Final Published Version (URL): http://informahealthcare.com/doi/abs/10.1517/14728222.2011.641533
• Title of Journal or Parent Work: Expert Opinion on Therapeutic Patents
• ISSN: 1354-3776
• Volume: 15
• Issue: 12
• Start Page: 1387
• End Page: 1403
• Grant/Funding Information: This work was supported by the Bachmann-Strauss Dystonia and Parkinson Foundation, National Institutes of Health R01 NS33592, and National Institutes of Health U54 NS067501.
• Keywords: dopamine; dystonia; basal ganglia; calcium; plasticity; cerebellum; mitochondria
• Research Categories: Health Sciences, Pharmacology; Health Sciences, General

Abstract

Introduction Dystonia is a neurological disorder associated with twisting motions and abnormal postures, which compromise normal movements and can be both painful and debilitating. It can affect a single body part (focal), several contiguous regions (segmental), or the entire body (generalized), and can arise as a result of numerous causes, both genetic and acquired. Despite the diversity of causes and manifestations, shared clinical features suggest that common mechanisms of pathogenesis may underlie many dystonias. Areas Covered This review identifies shared themes in etiologically-diverse dystonias on several biological levels. At the cellular level, abnormalities in the dopaminergic system, mitochondrial function, and calcium regulation are discussed. At the anatomical level, the roles of the basal ganglia and the cerebellum in dystonia are described. Global central nervous system dysfunction, with regard to aberrant neuronal plasticity, inhibition, and sensorimotor integration is also discussed. Using clinical data and data from animal models, this article seeks to highlight shared pathways that may be critical in understanding mechanisms and identifying novel therapeutic strategies in dystonia. Expert Opinion Identifying shared features of pathogenesis can provide insight into the biological processes that underlie etiologically-diverse dystonias, and can suggest novel targets for therapeutic intervention that may be effective in a broad group of affected individuals.