Figure 2

Alveolar structure disorder-associated ILD and ER stress. The (Endoplasmic Reticulum) ER and its protein maturation machinery allow the synthesis of mature secretory and membrane proteins with specific folded conformation. In situations of stress induced by genetic mutations or environmental factors, unfolded or misfolded proteins are retained in the ER and induce a defence mechanism called the ER stress response. The induction of ER chaperones is critical to increase the ER folding capacity allowing the production of correctly folded protein. When this defence mechanism is impaired, the misfolded proteins can either be degraded by the proteasome or form protein aggregates. Protein aggregates are toxic and can cause conformational diseases. Within the alveolar epithelium, misfolding of SP-C could trigger induction of intra-cellular aggregate formation and ER stress, with consequently development of alveolar structure disorder-associated ILD and conformational disease.