[The role of the adaptive stress response in the pathogenesis of neurodegenerative diseases, cancer and diabetes mellitus type 2]

Abstract

The ER (Endoplasmatic Reticulum) an intricate intracellular membrane system is responsible for many functions within cells; including folding and post-translational modifications of secretory proteins biosynthesis of ceramides, phospholipids and coordination of cell homeostasis. Perturbation of these ER processes leads to high levels unfolded and misfolded proteins within the lumen of the ER. These disturbances lead to activation of three primary receptors: PERK (Protein kinase RNA-like endoplasmic reticulum kinase), IRE1 (Inositol-Requiring-Enzyme 1) and ATF6 (Activating Transcription Factor 6). These signal transducers are responsible for inducing signalling pathways termed UPR (Unfolded Protein Response) restoring cell homeostasis. In contrast, unresolved ER stress contributes to cell death by apoptosis. Recent research allows for a conclusion that the deregulation of UPR is the main causative factor for functional cell loss and moreover, cell death by apoptosis, which is strictly linked to the pathology of human diseases to include: cancer, diabetes mellitus type 2 and neurodegenerative diseases such as Alzheimer's, Parkinson's and prion diseases.

Keywords: cancer; diabetes mellitus type 2; endoplasmatic reticulum stress; neurodegenerative diseases; unfolded protein response.