Compartimentspecifieke Remming van Synaptische Autofagie: Rab39-Gemedieerde Regulatie van Atg9-Vesikeltransport

Synapses, the primary sites of neuronal communication, are highly dynamic structures that require efficient mechanisms to maintain protein homeostasis. Unlike the soma, synapses must independently manage the clearance of dysfunctional proteins and organelles, particularly under stress conditions caused by synaptic activity. Disruptions in this process are strongly linked to neurodegenerative diseases, including Parkinson's disease (PD), where synaptic dysfunction is often an early pathological feature. Autophagy, a critical pathway for protein and organelle degradation, has emerged as a key mechanism in maintaining synaptic health. However, the regulation of synaptic autophagy and its interplay with other cellular processes, such as membrane trafficking, remain poorly understood. Recent studies suggest that EndophilinA (EndoA), a synapse-specific protein implicated in endocytosis, also plays a role in autophagosome formation at synapses. Given its interactions with PD-related proteins, EndoA may serve as a critical node linking synaptic autophagy to neurodegeneration. To identify novel genetic regulators of synaptic autophagy and neuroprotection, we aim to conduct a forward genetic screen using Drosophila as a model. This study will uncover key molecular pathways that regulate synaptic autophagy and provide new insights into therapeutic targets for neurodegenerative diseases.