Integration of cross-species multi-omics with in vivo experimental validation identifies Parkinson's disease therapeutic targets and novel risk factors within endolysosomal pathway subnetworks - PubMe
4 hours ago
- #Parkinson's disease
- #Therapeutic targets
- #Endolysosomal pathway
- Parkinson's disease (PD) is a common neurodegenerative movement disorder with increasing global healthcare impact.
- A key feature of PD is the accumulation of α-synuclein (αSyn) in intracellular inclusions like Lewy bodies.
- Genomic studies link PD risk factors to the endolysosomal pathway (ELP), crucial for protein and membrane recycling.
- Dysregulation in ELP components suggests its broad dysfunction contributes to PD pathogenesis.
- Targeted manipulation of specific ELP genes may offer therapeutic benefits against αSyn-induced pathology.
- An integrative multi-omic network approach identified dysregulated ELP subnetworks linked to PD risk factors.
- Experimental validation in a Drosophila model confirmed the role of these subnetworks in disease progression.
- Key subnetworks include Endosomal Sorting Complex Required for Transport (ESCRT) and phosphatidylinositol cycle genes.
- Manipulation of STAM1/2, INPP4A/B, and TMEM55A/B genes improved behavioral deficits and protected dopaminergic neurons.
- The study provides new insights into ELP dysfunction in PD and identifies novel therapeutic targets and risk factors.