ReviewProteostasis impairment in ALS

- Basic mechanisms of the ER homeostasis, ubiquitin proteasome system (UPS), and autophagy are overviewed.
- Discussion on how proteostasis impairment occurs in ALS.
- Relevance between ER stress and ALS-associated pathomechanisms.
- Discuss the roles and dysfunction of autophagy and UPS system in ALS.
- Discuss studies wherein amelioration of ALS pathophysiology was achieved by targeting proteostasis dysfunction in ALS.

In physiological conditions the maintenance of the cellular proteome is a prerequisite for optimal cell functioning and cell survival. Additionally, cells need to constantly sense and adapt to their changing environment and associated stressors. Cells achieve this via a set of molecular chaperones, protein clearance pathways as well as stress-associated signaling networks which work together to prevent protein misfolding, its aggregation and accumulation in subcellular compartments. These processes together form the proteostasis network which helps in maintaining cellular proteostasis. Imbalance or impairment in this processes is directly linked to ageing associated disorders such as diabetes, cancer, stroke, metabolic disorders, pulmonary fibrosis, inflammation and neurodegenerative diseases. In this review, we provide insights into the proteostasis process and how its failure governs neurodegenerative disorders with a special focus on Amyotrophic lateral sclerosis (ALS).This article is part of a Special Issue entitled SI:ER stress.