Proteostasis Failure in Neurodegenerative Diseases: Focus on Oxidative Stress

Topic: Disease mechanisms in lab and animal studies

Protein homeostasis or proteostasis is an essential balance of cellular protein levels mediated through an extensive network of biochemical pathways that regulate different steps of the protein quality control, from the synthesis to the degradation. All proteins in a cell continuously turn over, contributing to development, differentiation, and aging. Due to the multiple interactions and connections of proteostasis pathways, exposure to stress conditions may cause various types of protein damage, altering cellular homeostasis and disrupting the entire network with additional cellular stress. Furthermore, protein misfolding and/or alterations during protein synthesis results in inactive or toxic proteins, which may overload the degradation mechanisms. The maintenance of a balanced proteome, preventing the formation of impaired proteins, is accomplished by two major catabolic routes: the ubiquitin proteasomal system (UPS) and the autophagy-lysosomal system. The proteostasis network is particularly important in nondividing, long-lived cells, such as neurons, as its failure is implicated with the development of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. These neurological disorders share common risk factors such as aging, oxidative stress, environmental stress, and protein dysfunction, all of which alter cellular proteostasis, suggesting that general mechanisms controlling proteostasis may underlay the etiology of these diseases. In this review, we describe the major pathways of cellular proteostasis and discuss how their disruption contributes to the onset and progression of neurodegenerative diseases, focusing on the role of oxidative stress.

Key findings

• Furthermore, protein misfolding and/or alterations during protein synthesis results in inactive or toxic proteins, which may overload the degradation mechanisms.
• These neurological disorders share common risk factors such as aging, oxidative stress, environmental stress, and protein dysfunction, all of which alter cellular proteostasis, suggesting that general mechanisms controlling proteostasis may underlay the etiology of these diseases.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1155/2020/5497046
• PubMed: 32308803
• Original source →

Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.

@article{hohn2020-32308803,
  author  = {Höhn, Annika and Tramutola, Antonella and Cascella, Roberta},
  title   = {{Proteostasis Failure in Neurodegenerative Diseases: Focus on Oxidative Stress}},
  journal = {Oxidative medicine and cellular longevity},
  year    = {2020},
  doi     = {10.1155/2020/5497046},
  pmid    = {32308803},
  url     = {https://doi.org/10.1155/2020/5497046}
}

Related studies in Disease mechanisms

• The interplay between oxidative stress and autophagy: focus on the development of neurological diseases Behavioral and brain functions : BBF · 2022-01-29 · usefulness score 41/100
• Oxidative Stress: A Key Modulator in Neurodegenerative Diseases Molecules (Basel, Switzerland) · 2019-04-22 · usefulness score 41/100
• Oxidative Stress in Neurodegenerative Diseases: From Molecular Mechanisms to Clinical Applications Oxidative medicine and cellular longevity · 2017-07-12 · usefulness score 41/100
• Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options Current neuropharmacology · 2009-03-01 · usefulness score 40/100
• Oxidative stress, mitochondrial damage and neurodegenerative diseases Neural regeneration research · 2013-07-01 · usefulness score 40/100
• The Role of Oxidative Stress in Neurodegenerative Diseases Experimental neurobiology · 2015-10-12 · usefulness score 40/100

Also tagged “autophagy”

240 studies in the library carry the topic tag “autophagy”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 240 tagged studies.

• Aluminum neurotoxicity and autophagy: a mechanistic view Neurological research · 2022-10-08 · usefulness score 41/100 · Disease mechanisms
• Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons The Journal of neuroscience : the official journal of the Society for Neuroscience · 2000-05-01 · usefulness score 36/100 · Drug development
• CCDC50 mediates the clearance of protein aggregates to prevent cellular proteotoxicity Autophagy · 2024-07-30 · usefulness score 43/100 · Disease mechanisms

Similar studies

• Cellular Proteostasis in Neurodegeneration 2019 · Disease mechanisms
• Proteostasis in neurodegenerative diseases 2024 · Disease mechanisms
• Protein S-nitrosylation and oxidation contribute to protein misfolding in neurodegeneration 2021 · Disease mechanisms
• The ubiquitin-proteasome system in neurodegeneration 2014 · Disease mechanisms
• Protein Quality Control and the Amyotrophic Lateral Sclerosis/Frontotemporal Dementia Continuum 2017 · Disease mechanisms
• Glia-specific autophagy dysfunction in ALS 2020 · Disease mechanisms

More on Disease mechanisms

• A review that covers this ground Aging, energy, and oxidative stress in neurodegenerative diseases Annals of neurology · 1995-09-01 · usefulness score 40/100
• Newest in this subject Aβ42 oligomers disrupt calcium homeostasis via Piezo1 and induce neurotoxicity in differentiated SH-SY5Y cells Research Square · 2026-10-29 · Preprint — not yet peer-reviewed · usefulness score 16/100
• Newest in this subject Neuronal Hyperactivity Induces Tau Phosphorylation Selectively in Excitatory Pyramidal Neurons Which Contributes to GluA2 Regulation bioRxiv · 2026-10-28 · Preprint — not yet peer-reviewed · usefulness score 16/100

See all studies in Disease mechanisms →