Molecular and clinical prodrome of Parkinson disease: implications for treatment.
The development of interventions to slow or prevent progression represents an important aim for current research into Parkinson disease (PD). General agreement prevails that success in this endeavor will depend on a clearer understanding of etiology and pathogenesis, and several important advances have recently been made, particularly in defining the genetic causes of PD. Studies of the biochemical consequences of the mutations that cause familial PD, and postmortem brain studies of idiopathic, sporadic PD, have highlighted mitochondrial dysfunction, oxidative stress, and protein metabolism by the ubiquitin-proteasomal and autophagy systems as being central to pathogenesis. In parallel with advances in etiopathogenesis, a clearer perception has developed of the clinical prodrome of PD, offering an opportunity to identify individuals who are at risk of PD, as well as those in the earliest clinical phase of the disease that might even precede the onset of motor symptoms. These populations are potentially the most suitable in which to test new protective therapies, and to study potential peripheral markers of disease progression. The awareness of the early symptomatic period of PD also raises the possibility of providing treatments that not only improve motor function but might also favorably modify outcome.
Schapira
Anthony H V
AH
Department of Clinical Neurosciences, Institute of Neurology, University College Medical School, Rowland Hill Street, London NW3 2PF, UK. a.schapira@medsch.ucl.ac.uk
Tolosa
Eduardo
E
D000818:Animals; D001343:Autophagy / Q000502:physiology; D004777:Environment; D006801:Humans; D028361:Mitochondrial Diseases / Q000150:complications*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D010766:Phosphorylation / Q000502:physiology; D051843:Synucleins / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
D018696:Neuroprotective Agents; D051843:Synucleins; D025801:Ubiquitin