1. Figure 2 ER stress and proteostasis in neurodegenerative diseases
Figure 2 | ER stress and proteostasis in neurodegenerative diseases. Ageing, environmental factors and mutation of specific disease-related genes can trigger misfolding of a particular protein, leading to formation of aggregates that range from small oligomeric species to large inclusion bodies. This abnormal aggregation results in endoplasmic reticulum (ER) stress. ER stress can increase aggregation of disease-related proteins via a feedback loop by altering the folding and quality-control capacity of the cell or by altering the expression of disease-related genes. ER stress engages unfolded protein response (UPR) sensors that activate distinct downstream responses to improve protein folding and quality-control mechanisms to reduce ER stress. Long-term ER stress over-rides the adaptive responses of the UPR, and induces apoptosis. Chronic inhibition of protein synthesis can also reduce synthesis of synaptic proteins, thereby impairing neuronal function. ERAD, ER-associated degradation.
Hetz, C. & Saxena, S. (2017) ER stress and the unfolded protein response in neurodegeneration
Nat. Rev. Neurol. doi: /nrneurol