Cellular Proteostasis in Neurodegeneration

• Published in: Molecular neurobiology Vol. 56; no. 5; pp. 3676 - 3689
• Main Authors: Kurtishi, Alberim, Rosen, Benjamin, Patil, Ketan S., Alves, Guido W., Møller, Simon G.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-05-2019; Springer Nature B.V
• Subjects: Aging; Amyotrophic lateral sclerosis; Apoptosis; Autophagy; Biodegradation; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell death; Cellular stress response; Disease; Endoplasmic reticulum; Environmental stress; Neurobiology; Neurodegeneration; Neurodegenerative diseases; Neurology; Neurosciences; Oxidative stress; Phagocytosis; Post-translation; Protein biosynthesis; Protein folding; Protein sources; Protein synthesis; Proteins; Risk factors; Aggregation; Ubiquitin; Proteostasis; Neurodegeneration; Proteotoxicity; Chaperone; ROS; Autophagy; ER; Apoptosis; Lewy bodies
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-018-1334-z

The term proteostasis reflects the fine-tuned balance of cellular protein levels, mediated through a vast network of biochemical pathways. This requires the regulated control of protein folding, post-translational modification, and protein degradation. Due to the complex interactions and intersection of proteostasis pathways, exposure to stress conditions may lead to a disruption of the entire network. Incorrect protein folding and/or modifications during protein synthesis results in inactive or toxic proteins, which may overload degradation mechanisms. Further, a disruption of autophagy and the endoplasmic reticulum degradation pathway may result in additional cellular stress which could ultimately lead to cell death. Neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and Amyotrophic Lateral Sclerosis all share common risk factors such as oxidative stress, aging, environmental stress, and protein dysfunction; all of which alter cellular proteostasis. The differing pathologies observed in neurodegenerative diseases are determined by factors such as location-specific neuronal death, source of protein dysfunction, and the cell’s ability to counter proteotoxicity. In this review, we discuss how the disruption in cellular proteostasis contributes to the onset and progression of neurodegenerative diseases.