Efficient quality control mechanisms are essential for a healthy, functional neuron. Recognition and degradation of misfolded, damaged, or potentially toxic proteins, is a crucial aspect of protein quality control. Tau is a protein that is highly expressed in neurons, and plays an important role in modulating a number of physiological processes. Maintaining appropriate levels of tau is key for neuronal health; hence perturbations in tau clearance mechanisms are likely significant contributors to neurodegenerative diseases such as Alzheimer's disease and frontotemporal lobar degeneration. In this chapter we will first briefly review the two primary degradative mechanisms that mediate tau clearance: the proteasome system and the autophagy-lysosome pathway. This will be followed by a discussion about what is known about the contribution of each of these pathways to tau clearance. We will also present recent findings on tau degradation through the endolysosomal system. Further, how deficits in these degradative systems may contribute to the accumulation of dysfunctional or toxic forms of tau in neurodegenerative conditions is considered.
Keywords: Autophagy; Autophagy receptors; BAG3; Endolysosomal pathway; Proteasome; Ubiquitylation.