Diagnosis and treatment of Parkinson disease: molecules to medicine

J Clin Invest. 2006 Jul;116(7):1744-54. doi: 10.1172/JCI29178.

Abstract

Parkinson disease (PD) is a relatively common disorder of the nervous system that afflicts patients later in life with tremor, slowness of movement, gait instability, and rigidity. Treatment of these cardinal features of the disease is a success story of modern science and medicine, as a great deal of disability can be alleviated through the pharmacological correction of brain dopamine deficiency. Unfortunately these therapies only provide temporary, though significant, relief from early symptoms and do not halt disease progression. In addition, pathological changes outside of the motor system leading to cognitive, autonomic, and psychiatric symptoms are not sufficiently treated by current therapies. Much as the discovery of dopamine deficiency led to powerful treatments for motor symptoms, recent discoveries concerning the role of specific genes in PD pathology will lead to the next revolution in disease therapy. Understanding why and how susceptible cells in motor and nonmotor regions of the brain die in PD is the first step toward preventing this cell death and curing or slowing the disease. In this review we discuss recent discoveries in the fields of diagnosis and treatment of PD and focus on how a better understanding of disease mechanisms gained through the study of monogenetic forms of PD has provided novel therapeutic targets.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Disease Progression
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Mitochondria / metabolism
  • Neuroprotective Agents / metabolism
  • Neuroprotective Agents / therapeutic use
  • Oncogene Proteins / metabolism
  • Oxidative Stress
  • Parkinson Disease / diagnosis*
  • Parkinson Disease / pathology
  • Parkinson Disease / physiopathology
  • Parkinson Disease / therapy*
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Deglycase DJ-1
  • Protein Kinases / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • alpha-Synuclein / metabolism

Substances

  • Intracellular Signaling Peptides and Proteins
  • Neuroprotective Agents
  • Oncogene Proteins
  • Ubiquitin
  • alpha-Synuclein
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Protein Kinases
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • PTEN-induced putative kinase
  • Protein Serine-Threonine Kinases
  • PARK7 protein, human
  • Protein Deglycase DJ-1
  • Proteasome Endopeptidase Complex