Diagnosis and treatment of Parkinson disease: molecules to medicine.
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.
Savitt
Joseph M
JM
Institute for Cell Engineering, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Dawson
Valina L
VL
Dawson
Ted M
TM
D018450:Disease Progression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008928:Mitochondria / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000627:therapeutic use; D015513:Oncogene Proteins / Q000378:metabolism; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
D047908:Intracellular Signaling Peptides and Proteins; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D018696:Neuroprotective Agents; D015513:Oncogene Proteins; D046988:Proteasome Endopeptidase Complex; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein; C495280:LRRK2 protein, human; C105131:PARK7 protein, human