SUMMARY
# Autophagy Enhancement Drug Screening for Neurodegeneration
## Background and Rationale
Autophagy represents one of the most fundamental cellular quality control mechanisms, serving as a critical cellular housekeeping pathway that becomes increasingly vital as organisms age and face mounting proteostatic stress. This evolutionary conserved process involves the sequestration of damaged organelles, misfolded proteins, and cellular debris within double-membrane vesicles called autophagosomes, whic
METHODOLOGY NOTES
**Phase 1: Patient Recruitment and Baseline Assessment (Months 1-6)**
• Recruit 240 participants: 60 AD patients (MMSE 18-26), 60 PD patients (Hoehn-Yahr stage 1-3), 60 FTD patients (CDR 0.5-2), 60 age-matched healthy controls
• Obtain informed consent and ethics approval from institutional review boards
• Perform comprehensive neuropsychological testing (MMSE, MoCA, CDR, UPDRS for PD)
• Collect baseline biosamples: CSF (15ml), plasma (20ml), peripheral blood mononuclear cells (50ml)
• Conduct baseline neuroimaging: structural MRI, tau-PET, amyloid-PET imaging
• Establish autophagy biomarker baseline: LC3-II/LC3-I ratio, p62/SQSTM1 levels, LAMP1 expression
**Phase 2: Drug Screening Platform Development (Months 3-8)**
• Generate patient-derived induced pluripotent stem cells (iPSCs) from 20 participants per disease group
• Differentiate iPSCs to cortical neurons, dopaminergic neurons, and motor neurons using established protocols
• Validate disease-specific phenotypes: Aβ accumulation