ReviewER chaperones in neurodegenerative disease: Folding and beyond

- Role of the ER chaperon network in physiological and pathological conditions.
- ER chaperons and foldases contribution to proteostasis maintenance is critical.
- Evidence placing ER chaperons as key players in synaptic function.
- Protein disulfide isomerase family and ER chaperones participates in neurodegenerative diseases.

Proteins along the secretory pathway are co-translationally translocated into the lumen of the endoplasmic reticulum (ER) as unfolded polypeptide chains. Afterwards, they are usually modified with N-linked glycans, correctly folded and stabilized by disulfide bonds. ER chaperones and folding enzymes control these processes. The accumulation of unfolded proteins in the ER activates a signaling response, termed the unfolded protein response (UPR). The hallmark of this response is the coordinated transcriptional up-regulation of ER chaperones and folding enzymes. In order to discuss the importance of the proper folding of certain substrates we will address the role of ER chaperones in normal physiological conditions and examine different aspects of its contribution in neurodegenerative disease.This article is part of a Special Issue entitled SI:ER stress.