Parkinson's Disease

What it is

Parkinson’s disease (PD) is the second most common neurodegenerative disease. Pathology: progressive loss of dopaminergic neurons in the substantia nigra pars compacta, with intracellular Lewy bodies (mainly α-synuclein aggregates). Clinically: bradykinesia, resting tremor, rigidity, postural instability, plus non-motor features (sleep disturbance, autonomic dysfunction, cognitive decline, mood disorders).

Risk and protective factors

• Age — the single biggest factor.
• Genetic: GBA, LRRK2, PINK1, PRKN, SNCA mutations explain a minority.
• Pesticide exposure (paraquat, rotenone).
• Head injury history.
• Inverse association with coffee, smoking (causality uncertain), exercise, and possibly NSAIDs.

Mechanism

Mitochondrial dysfunction (PINK1/Parkin pathway, complex I inhibition), impaired autophagy/mitophagy, proteostatic failure of α-synuclein clearance, neuroinflammation.

Treatments

• Levodopa/carbidopa: gold standard for motor symptoms; eventual motor fluctuations.
• Dopamine agonists, MAO-B inhibitors, COMT inhibitors.
• Deep brain stimulation for selected patients with motor fluctuations.
• Focused ultrasound thalamotomy for tremor.
• Disease-modifying therapies remain elusive; multiple agents in trials including α-synuclein-directed antibodies.

Lifestyle relevance

Vigorous exercise (especially high-intensity treadmill) has the strongest evidence for slowing functional decline in early PD.

Related entries

Mitophagy, Mitochondrial dysfunction, Loss of proteostasis.