A proteostasis view of neurodegeneration (ND) identifies protein aggregation as 
a leading causative reason for damage seen at the cellular and organ levels. 
While investigative therapies that aim at dissolving aggregates have failed, and 
the promises of silencing expression of ND associated pathogenic proteins or the 
deployment of engineered induced pluripotent stem cells (iPSCs) are still in the 
horizon, emerging literature suggests degrading aggregates through 
autophagy-related mechanisms hold the current potential for a possible cure. 
Macroautophagy (hereafter autophagy) is an intracellular degradative pathway 
where superfluous or unwanted cellular cargoes (such as peroxisomes, 
mitochondria, ribosomes, intracellular bacteria and misfolded protein 
aggregates) are wrapped in double membrane vesicles called autophagosomes that 
eventually fuses with lysosomes for their degradation. The selective branch of 
autophagy that deals with identification, capture and degradation of protein 
aggregates is called aggrephagy. Here, we cover the workings of aggrephagy 
detailing its selectivity towards aggregates. The diverse cellular adaptors that 
bridge the aggregates with the core autophagy machinery in terms of 
autophagosome formation are discussed. In ND, essential protein quality control 
mechanisms fail as the constituent components also find themselves trapped in 
the aggregates. Thus, although cellular aggrephagy has the potential to be 
upregulated, its dysfunction further aggravates the pathogenesis. This 
phenomenonwhen combined with the fact that neurons can neither dilute out the 
aggregates by cell division nor the dead neurons can be replaced due to low 
neurogenesis, makes a compelling case for aggrephagy pathway as a potential 
therapeutic option.