Many major neurodegenerative diseases are associated with proteins misfolding and aggregation, which are also called “neurodegenerative conformational disease”.  The interaction of gene mutation and  environmental factors are probably primary events resulting in oligomer and aggregate formations of proteins.  Moreover, the dysfunctions of protein control systems, i.e. the ubiquitin-proteasome system and autophagy- lysosomal system, also contribute to the neurodegenerative process.  The present review mainly summarizes  protein misfolding and aggregation in the development of neurodegenerative conformational disease and the  underling mechanisms, as well as upregulation of heat shock proteins as a promising treatment method for  this kind of disease.