The neurobiological basis for novel experimental therapeutics in dystonia

NEUROBIOLOGY OF DISEASE

卷:130

Review

Downs, Anthony M.¹  Roman, Kaitlyn M.¹  Campbell, Simone A.¹  Pisani, Antonio^2,3  Hess, Ellen J.^1,4  Bionsi, Paola² 

[1] Emory Univ, Sch Med, Dept Pharmacol & Chem Biol, Atlanta, GA 30322 USA

[2] IRCCS Fdn Santa Lucia, Lab Neurophysiol & Plast, I-00143 Rome, Italy

[3] Univ Roma Tor Vergata, Dept Syst Med, I-00133 Rome, Italy

[4] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA

关键词: Basal ganglia;    Cerebellum;    Drug discovery;    Anatomy;    Therapy;    Animal models;   

DOI  :  10.1016/j.nbd.2019.104526

来源: Elsevier

【 摘 要 】

Dystonia is a movement disorder characterized by involuntary muscle contractions, twisting movements, and abnormal postures that may affect one or multiple body regions. Dystonia is the third most common movement disorder after Parkinson's disease and essential tremor. Despite its relative frequency, small molecule therapeutics for dystonia are limited. Development of new therapeutics is further hampered by the heterogeneity of both clinical symptoms and etiologies in dystonia. Recent advances in both animal and cell-based models have helped clarify divergent etiologies in dystonia and have facilitated the identification of new therapeutic targets. Advances in medicinal chemistry have also made available novel compounds for testing in biochemical, physiological, and behavioral models of dystonia. Here, we briefly review motor circuit anatomy and the anatomical and functional abnormalities in dystonia. We then discuss recently identified therapeutic targets in dystonia based on recent preclinical animal studies and clinical trials investigating novel therapeutics.

【 授权许可】

Free