Proteomic analysis of protein homeostasis and aggregation
Ewa Laskowska , Dorota Kuczyńska-Wiśnik , Barbara Lipińska
AbstractProtein homeostasis (proteostasis) refers to the ability of cells to preserve the correct balance between protein synthesis, folding and degradation. Proteostasis is essential for optimal cell growth and survival under stressful conditions. Various extracellular and intracellular stresses including heat shock, oxidative stress, proteasome malfunction, mutations and aging-related modifications can result in disturbed proteostasis manifested by enhanced misfolding and aggregation of proteins. To limit protein misfolding and aggregation cells have evolved various strategies including molecular chaperones, proteasome system and autophagy. Molecular chaperones assist folding of proteins, protect them from denaturation and facilitate renaturation of the misfolded polypeptides, whereas proteasomes and autophagosomes remove the irreversibly damaged proteins. The impairment of proteostasis results in protein aggregation that is a major pathological hallmark of numerous age-related disorders, such as cataract, Alzheimer’s, Parkinson’s, Huntington’s, and prion diseases. To discover protein markers and speed up diagnosis of neurodegenerative diseases accompanied by protein aggregation, proteomic tools have increasingly been used in recent years. Systematic and exhaustive analysis of the changes that occur in the proteomes of affected tissues and biofluids in humans or in model organisms is one of the most promising approaches to reveal mechanisms underlying protein aggregation diseases, improve their diagnosis and develop therapeutic strategies. Significance: In this review we outline the elements responsible for maintaining cellular proteostasis and present the overview of proteomic studies focused on protein-aggregation diseases. These studies provide insights into the mechanisms responsible for age–related disorders and reveal new potential biomarkers for Alzheimer’s, Parkinson’s, Huntigton’s and prion diseases.
|Journal series||Journal of Proteomics, ISSN 1874-3919, (A 35 pkt)|
|Publication size in sheets||0.7|
|Keywords in English||proteostasis, heat shock proteins, protein aggregation diseases, biomarkers|
|Score||= 35.0, 24-07-2019, ArticleFromJournal|
|Publication indicators||: 2017 = 0.982; : 2017 = 3.722 (2) - 2017=3.725 (5)|
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