Cellular Proteostasis in Neurodegeneration
Autor: | Ketan S. Patil, Simon Geir Møller, Benjamin Rosen, Guido Alves, Alberim Kurtishi |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Neuroscience (miscellaneous) Biology Protein degradation Protein Aggregates 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Ubiquitin medicine Animals Humans Endoplasmic reticulum Neurodegeneration Autophagy Endoplasmic Reticulum Stress medicine.disease Mitochondria Cell biology 030104 developmental biology Proteostasis Neurology Proteotoxicity Chaperone (protein) Nerve Degeneration biology.protein Protein Processing Post-Translational 030217 neurology & neurosurgery |
Zdroj: | Molecular Neurobiology. 56:3676-3689 |
ISSN: | 1559-1182 0893-7648 |
Popis: | 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. |
Databáze: | OpenAIRE |
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