The elimination of accumulated and aggregated proteins: a role for aggrephagy in neurodegeneration

The presence of ubiquitinated protein inclusions is a hallmark of most adult onset neurodegenerative disorders. Although the toxicity of these structures remains controversial, their prolonged presence in neurons is indicative of some failure in fundamental cellular processes. It therefore may be possible that driving the elimination of inclusions can help re-establish normal cellular function. There is growing evidence that macroautophagy has two roles; first, as a non-selective degradative response to cellular stress such as starvation, and the other as a highly selective quality control mechanism whose basal levels are important to maintain cellular health. One particular form of macroautophagy, aggrephagy, may have particular relevance in neurodegeneration, as it is responsible for the selective elimination of accumulated and aggregated ubiquitinated proteins. In this review, we will discuss the molecular mechanisms and role of protein aggregation in neurodegeneration, as well as the molecular mechanism of aggrephagy and how it may impact disease. This article is part of a Special Issue entitled "Autophagy and protein degradation in neurological diseases."