Cell Communication Insights

‘Proteinopathy’ refers to a class of diseases where the aggregation of misfolded or non-native proteins/inclusion bodies is identified to be the underlying cause. Most neurodegenerative diseases feature such non-native protein aggregates or inclusion bodies. Over 4 decades of research on Alzheimer disease and various other neurodegenerative diseases has highlighted the importance of an articulate and precise proteostasis machinery in protein quality control. This proteostasis machinery exists both within and outside the cells. A great number of studies have elucidated the role of intracellular chaperones in guiding the process of folding and clearance of native and non-native proteins. However, our idea about the mechanism and processes involved in regulation of proteostasis by extracellular chaperones is still largely unknown. In addition, the process of proteostasis differs within the cell types; for example, different populations of neuronal cells are known for selective vulnerability to physiological stress. This review focusses on the extracellular chaperones, their role in protein quality control, and their effect on neuronal structure, function, and survivability.