Liaisons dangereuses: autophagy, neuronal survival and neurodegeneration

Abstract

Neurons are complex differentiated cells with specialised, polarised membrane domains. Their function and viability is intimately linked to the availability of trophic factors, but ultimately depends on active membrane transport connecting axons and dendrites with the distant cell body. Neurons, because of their extreme polarisation, size and post-mitotic nature may be uniquely sensitive to the accumulation of damaged or aggregated cytosolic proteins, or membranes, and rely on autophagy for survival. Autophagy is a highly conserved, ubiquitous lysosomal degradative process, which plays an important role in cell homeostasis in both normal growth settings, and abnormal, stressful conditions. Although recent evidence supports this assumption, how autophagy protects cells from damage leading to neurodegeneration is not yet clear.