Purinergic Signaling Dysfunction Validation in Parkinson's Disease

SUMMARY

# Purinergic Signaling Dysfunction Validation in Parkinson's Disease ## Background and Rationale Purinergic signaling dysfunction represents a compelling upstream mechanism in Parkinson's disease pathogenesis, with mounting evidence suggesting that disrupted ATP and adenosine receptor signaling may serve as a primary trigger for α-synuclein aggregation, neuroinflammation, and dopaminergic neurodegeneration. The purinergic system encompasses a complex network of P1 adenosine receptors (A1, A2A, A

METHODOLOGY NOTES

**Phase 1: Patient Recruitment and Baseline Assessment (Months 1-6)** • Recruit 120 early-stage PD patients (Hoehn & Yahr stages 1-2) from movement disorder clinics • Recruit 80 age-matched healthy controls and 40 patients with other neurodegenerative diseases • Obtain informed consent and collect demographic data, medical history, and medication records • Perform comprehensive neurological assessment including MDS-UPDRS III, cognitive testing (MoCA), and motor function evaluation • Collect baseline blood samples (50mL) for plasma ATP, adenosine, and purinergic receptor expression analysis • Perform lumbar puncture for CSF collection (15mL) to measure ATP, adenosine, P2X7, A2A receptor levels, and alpha-synuclein species • Conduct neuroimaging including DaTscan SPECT and high-resolution structural MRI **Phase 2: Purinergic Biomarker Analysis (Months 4-12)** • Process plasma samples using HPLC-MS/MS for ATP and adenosine quantification (detection limit: 0.1 μM) • Perform flow cytometry