title: Rational drug discovery design approaches for treating Parkinson's disease.
abstract: BACKGROUND
  Parkinson's disease (PD) is a severe progressive neurodegenerative disorder. As yet, no therapeutic agent can prevent the characteristic neuronal cell loss in PD brain. The introduction of levodopa to the clinic several decades ago has greatly mitigated the symptomatic burden in PD patients. But the discovery of neuroprotective and disease-modifying therapies has lagged behind, becoming one of the most desired prizes in the drug discovery arms race for neurodegenerative disorders, including PD.
  
  
  METHODS
  In this review, the author provides an overview of the rational drug discovery approaches that are designed to prevent the onset or alter the course of the disease, and/or target its non-motor symptoms.
  
  
  CONCLUSIONS
  Largely due to the intertwined etiology that is a hallmark of PD's pathology, neuroprotective drug discovery is challenging, while very limited targeting strategies exist for the non-motor symptoms that afflict sufferers of PD. Rational approaches toward PD neurotherapeutics should target previously identified or emerging pathological pathways that are discovered in the course of investigating the underlying mechanisms in PD disease progression. Each of these pathways contributes to events that ultimately lead to the complex disease burden seen in PD and can form the basis for rational and highly targeted drug development.
authors.affiliation: Idaho State University, College of Pharmacy, Graduate School, Department of Biomedical and Pharmaceutical Sciences , 921 S. 8th Avenue, Pocatello, ID 83209-0001 , USA +1 208 282 2490 ; vanderschyf@isu.edu.
authors.forename: Cornelis J
authors.initials: CJ
authors.lastname: Van der Schyf
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018450:Disease Progression; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D058990:Molecular Targeted Therapy; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000978:Antiparkinson Agents; D018696:Neuroprotective Agents
keywords: Parkinson’s disease; drug discovery; motor deficits; neurodegeneration; neuroprotection; neurorescue; non-motor symptoms; pathoetiological pathways