S4 Neuronal Autophagy - Implications for Disease and Therapy
Christian Behl (Mainz) and Michael Sendtner (Würzburg)
Live Discussion: Monday, March 22, 2021, 18:00 - 19:00h
Proper function of the nervous system depends on mechanisms neurons employ to adapt their activity within synaptic networks. Here, the synthesis of new proteins but also protein degradation play an important role. Autophagy is a phylogenetically highly conserved cellular recycling process. Under basal (physiological) and stress (pathophysiological) conditions, it takes part in protein homeostasis and organelle control. Different selective and tightly controlled autophagy types are known, including the so-called macroautophagy. Currently, macroautophagy is being intensively studied in regards to cargo-selectivity and subtypes, such as aggrephagy (targeting aggregated proteins), mitophagy (targeting defective mitochondria), xenophagy (targeting pathogens) or ER-phagy (targeting ER subcompartments). Macroautophagy is of special importance for post-mitotic cells such as neurons and required for neurodevelopmental processes, neuronal homeostasis, and maintenance of neuronal function. Alterations in the autophagic-lysosomal pathway and vesicular trafficking have been described as early events in the pathogenesis of neurodegenerative disease. Moreover, many overlapping genes/pathways have been identified between autophagy regulation and neurodegenerative disorders, including Alzheimer’s disease, Amyotrophic Lateral Sclerosis, and Parkinson’s disease. Neurons with their specific morphology display compartment-specific types of autophagy, and autophagy in the presynaptic compartment is particularly important for synaptic homeostasis and most likely for plasticity processes. Autophagosomes, cargo-sequestering initial autophagy vesicles, are retrogradely transported in axons and their turnover is strongly linked to axonal transport processes. Mechanisms of how autophagy contributes to the turnover of vesicular membranes and proteins in the presynaptic compartment are topic of current research.
In this symposium, the process of autophagy in neurons will be presented and put into the context of the role of autophagy and proteostasis in synaptic function and neurodegenerative disease. New possible protective approaches targeting autophagy in neuronal cells will be discussed.
We gratefully acknowledge the financial support of RWD.