SUMMARY
# Sirtuin Dysfunction Validation in Parkinson's Disease
## Background and Rationale
Parkinson's disease (PD) is characterized by progressive neurodegeneration with accumulating evidence implicating mitochondrial dysfunction and impaired protein quality control. The Sirtuin Dysfunction Hypothesis proposes that dysregulation of NAD+-dependent sirtuin deacetylases contributes to PD pathogenesis through compromised mitochondrial biogenesis, defective autophagy, and increased oxidative stress. This c
METHODOLOGY NOTES
Phase 1 (Months 1-12): Recruit 120 PD patients (Hoehn-Yahr stages I-III) and 80 age-matched controls. Collect fasting blood samples at baseline and 6 months. Isolate PBMCs using Ficoll gradient centrifugation. Measure SIRT1, SIRT2, SIRT3 activities using fluorometric deacetylase assays. Quantify NAD+/NADH ratios via enzymatic cycling assays. Assess mitochondrial function using Seahorse XF analyzer measuring oxygen consumption rates. Evaluate autophagy markers (LC3-II/I ratio, p62 levels) by Western blot. Perform plasma metabolomics focusing on NAD+ biosynthesis pathway. Clinical assessments include UPDRS-III, MoCA, and PDQ-39 quality of life scores. Phase 2 (Months 13-24): Randomize 80 PD patients to resveratrol (1000mg daily) or placebo for 24 weeks. Primary endpoint: change in UPDRS-III motor scores. Secondary endpoints include cognitive testing, biomarker changes, and safety monitoring. Blood sampling at weeks 0, 4, 12, and 24 for sirtuin activities and NAD+ levels. Statistical anal