Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Diagnosis and treatment of Parkinson disease: molecules to medicine
Joseph M. Savitt, … , Valina L. Dawson, Ted M. Dawson
Joseph M. Savitt, … , Valina L. Dawson, Ted M. Dawson
Published July 3, 2006
Citation Information: J Clin Invest. 2006;116(7):1744-1754. https://doi.org/10.1172/JCI29178.
View: Text | PDF
Science in Medicine

Diagnosis and treatment of Parkinson disease: molecules to medicine

  • Text
  • PDF
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.

Authors

Joseph M. Savitt, Valina L. Dawson, Ted M. Dawson

×

Figure 1

Model of dopaminergic cell death and possible sites for therapeutic intervention in PD.

Options: View larger image (or click on image) Download as PowerPoint
Model of dopaminergic cell death and possible sites for therapeutic inte...
Studies on inherited forms of PD have led to the identification of genes that, when mutated, lead to dopaminergic cell loss. These genes are involved in a variety of cellular processes that include protein ubiquitination and degradation via the proteasome, response to oxidative stress, protein phosphorylation, mitochondrial function, and protein folding. Potential points of therapeutic intervention are highlighted: gene silencing therapies to reduce synuclein levels (i); inhibitors of synuclein aggregation and/or processing (ii); interventions to downregulate toxic substrates or upregulate parkin or proteasomal function (iii); interventions to enhance mitochondrial function with factors such as CoQ10, DJ-1, or PINK-1 (iv); free radical scavengers and antioxidants (v); kinase inhibitors to block LRRK2 activity or interventions to increase PINK-1 function (vi); and other therapies using trophic factors such as GDNF, survival genes, or fetal/stem cell replacement that would protect or replace susceptible cells (vii).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts