Proteostasis Disturbances and Inflammation in Neurodegenerative Diseases.
Cells
; 9(10)2020 09 28.
Article
em En
| MEDLINE
| ID: mdl-32998318
ABSTRACT
Protein homeostasis (proteostasis) disturbances and inflammation are evident in normal aging and some age-related neurodegenerative diseases. While the proteostasis network maintains the integrity of intracellular and extracellular functional proteins, inflammation is a biological response to harmful stimuli. Cellular stress conditions can cause protein damage, thus exacerbating protein misfolding and leading to an eventual overload of the degradation system. The regulation of proteostasis network is particularly important in postmitotic neurons due to their limited regenerative capacity. Therefore, maintaining balanced protein synthesis, handling unfolding, refolding, and degrading misfolded proteins are essential to preserve all cellular functions in the central nervous sysytem. Failing proteostasis may trigger inflammatory responses in glial cells, and the consequent release of inflammatory mediators may lead to disturbances in proteostasis. Here, we review the mechanisms of proteostasis and inflammatory response, emphasizing their role in the pathological hallmarks of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Furthermore, we discuss the interplay between proteostatic stress and excessive immune response that activates inflammation and leads to dysfunctional proteostasis.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
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Doenças Neurodegenerativas
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Doença de Alzheimer
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Proteostase
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article