Parkinson's Disease: The Epidemiology, Risk Factors, Molecular Pathogenesis, Prevention, and Therapy

Area of Science:

• Neuroscience
• Pathology
• Genetics

Background:

• Parkinson's disease (PD) is a progressive neurodegenerative disorder with increasing global prevalence.
• Current treatments for PD primarily manage symptoms due to incomplete understanding of disease mechanisms, particularly alpha-synuclein aggregation.
• A comprehensive understanding of PD's multifaceted nature is crucial for developing effective therapies.

Purpose of the Study:

• To provide an integrated overview of Parkinson's disease, encompassing epidemiological, etiological, pathophysiological, and clinical aspects.
• To explore established and emerging risk factors, including environmental, lifestyle, and gut microbiota influences.
• To review current and novel therapeutic strategies for Parkinson's disease.

Main Methods:

• Literature review integrating epidemiological, etiological, and pathophysiological data on Parkinson's disease.
• Analysis of molecular mechanisms, including proteostasis, oxidative stress, neuroinflammation, and metabolic dysfunctions.
• Evaluation of peripheral-central pathways (gut-brain, erythrocyte-brain, kidney-brain axes) in PD pathogenesis.

Main Results:

• Identified key risk factors such as environmental toxins, lifestyle, and gut dysbiosis.
• Highlighted the role of peripheral-central axes in contributing to PD pathogenesis.
• Detailed molecular disruptions including proteostatic failure, neuroinflammation, and metabolic alterations.

Conclusions:

• Understanding systemic pathophysiology and molecular dysregulations is key to linking PD mechanisms with clinical phenotypes.
• Microbiome-targeted and blood-based interventions show promise for Parkinson's disease management.
• Emerging biomarkers from microbial, inflammatory, and erythrocyte pathways may enable early diagnosis and disease modification.