New genetic insights highlight 'old' ideas on motor dysfunction in dystonia

Trends Neurosci. 2013 Dec;36(12):717-25. doi: 10.1016/j.tins.2013.09.003. Epub 2013 Oct 18.


Primary dystonia is a poorly understood but common movement disorder. Recently, several new primary dystonia genes were identified that provide new insight into dystonia pathogenesis. The GNAL dystonia gene is central for striatal responses to dopamine (DA) and is a component of a molecular pathway already implicated in DOPA-responsive dystonia (DRD). Furthermore, this pathway is also dysfunctional and pathogenically linked to mTOR signaling in L-DOPA-induced dyskinesias (LID). These new data suggest that striatal DA responses are central to primary dystonia, even when symptoms do not benefit from DA therapies. Here we integrate these new findings with current understanding of striatal microcircuitry and other dystonia-causing insults to develop new ideas on the pathophysiology of this incapacitating movement disorder.

Keywords: GNAL/Gα(olf); dopamine; dystonia; mTOR; signal transduction; striatum.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology
  • Dopamine / metabolism*
  • Dystonia / chemically induced
  • Dystonia / genetics*
  • Dystonia / pathology
  • Dystonia / physiopathology*
  • GTP-Binding Protein alpha Subunits / genetics*
  • Humans
  • Levodopa / adverse effects
  • Molecular Chaperones / genetics
  • Mutation / genetics
  • TOR Serine-Threonine Kinases / genetics


  • GTP-Binding Protein alpha Subunits
  • Molecular Chaperones
  • TOR1A protein, human
  • olfactory G protein subunit alpha olf
  • Levodopa
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Dopamine