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Triggers, Facilitators, and Aggravators: Redefining Parkinson's Disease Pathogenesis
Michaela E Johnson1, Benjamin Stecher2, Viviane Labrie3
1Center for Neurodegenerative Science, Van Andel Research Institute, 333 Bostwick Avenue, NE, Grand Rapids, MI 49503, USA; These authors contributed equally to this work.
Trends in Neurosciences
|October 22, 2018
Summary
Parkinson's disease pathogenesis involves three phases: triggers, facilitators, and aggravators. Targeting therapies to these distinct stages may improve clinical trial effectiveness for Parkinson's disease.
Area of Science:
- Neuroscience
- Pathology
- Clinical Medicine
Background:
- Parkinson's disease (PD) is a complex neurodegenerative disorder.
- Current understanding of PD pathogenesis lacks a clear temporal framework.
- Identifying distinct phases of PD development is crucial for effective treatment.
Purpose of the Study:
- To propose a three-phase model for Parkinson's disease pathogenesis.
- To delineate the roles of triggers, facilitators, and aggravators in PD progression.
- To inform the design of future clinical trials for Parkinson's disease.
Main Methods:
- Conceptual framework development based on existing literature.
- Hypothesized roles of environmental factors, inflammation, and molecular mechanisms.
- Analysis of potential therapeutic targets within each proposed phase.
Main Results:
- Proposed three distinct temporal phases of PD pathogenesis: triggers, facilitators, and aggravators.
- Identified potential triggers (viral infections, toxins) and facilitators (peripheral inflammation).
- Highlighted key aggravators including impaired autophagy and alpha-synuclein propagation.
Conclusions:
- Parkinson's disease progression can be understood through a three-phase model.
- Therapeutic strategies should be tailored to specific phases of PD.
- This phased approach may enhance the efficacy of clinical interventions for Parkinson's disease.