The Immunoproteasome in oxidative stress, aging, and disease

Johnston-Carey, Helen K.; Pomatto, Laura C.D.; Davies, Kelvin J.A.

doi:10.3109/10409238.2016.1172554

Cited by 84 publications

(90 citation statements)

References 129 publications

(202 reference statements)

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“…On the other hand, i20S shows higher proteolytic activity towards oxidized proteins compared to 20S [120]. In inflammatory processes, always accompanied by oxidative stress and therefore increased protein oxidation, the immunoproteasome and its co-expressed 11S regulator contribute significantly to preserving functional proteostasis [121].…”

Section: Proteostasis In Agingmentioning

confidence: 99%

Happily (n)ever after: Aging in the context of oxidative stress, proteostasis loss and cellular senescence

et al. 2017

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Aging is a complex phenomenon and its impact is becoming more relevant due to the rising life expectancy and because aging itself is the basis for the development of age-related diseases such as cancer, neurodegenerative diseases and type 2 diabetes. Recent years of scientific research have brought up different theories that attempt to explain the aging process. So far, there is no single theory that fully explains all facets of aging. The damage accumulation theory is one of the most accepted theories due to the large body of evidence found over the years. Damage accumulation is thought to be driven, among others, by oxidative stress. This condition results in an excess attack of oxidants on biomolecules, which lead to damage accumulation over time and contribute to the functional involution of cells, tissues and organisms. If oxidative stress persists, cellular senescence is a likely outcome and an important hallmark of aging. Therefore, it becomes crucial to understand how senescent cells function and how they contribute to the aging process. This review will cover cellular senescence features related to the protein pool such as morphological and molecular hallmarks, how oxidative stress promotes protein modifications, how senescent cells cope with them by proteostasis mechanisms, including antioxidant enzymes and proteolytic systems. We will also highlight the nutritional status of senescent cells and aged organisms (including human clinical studies) by exploring trace elements and micronutrients and on their importance to develop strategies that might increase both, life and health span and postpone aging onset.

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Section: Proteostasis In Agingmentioning

confidence: 99%

Happily (n)ever after: Aging in the context of oxidative stress, proteostasis loss and cellular senescence

et al. 2017

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“…Whether the increase of i20S formation is a cause or a result of the pathology is still under discussion. Most likely, i20S is induced to cope with a shifted proteostasis, especially during and after phases of oxidative shifts/stress [70] . Diseases accompanied by increased formation of i20S are age-related macular degeneration (AMD), neurodegenerative pathologies such as Alzheimer’s, Huntington’s and Parkinson’s, as well as amyotrophic lateral sclerosis (ALS) – all of them showing inflammatory aspects, such as enhanced ROS formation, protein oxidation, lipid peroxidation, or formation of advanced glycation end products (AGEs).…”

Section: Proteostasis Maintenance Systemsmentioning

confidence: 99%

Proteostasis, oxidative stress and aging

et al. 2017

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The production of reactive species is an inevitable by-product of metabolism and thus, life itself. Since reactive species are able to damage cellular structures, especially proteins, as the most abundant macromolecule of mammalian cells, systems are necessary which regulate and preserve a functional cellular protein pool, in a process termed “proteostasis”. Not only the mammalian protein pool is subject of a constant turnover, organelles are also degraded and rebuild. The most important systems for these removal processes are the “ubiquitin-proteasomal system” (UPS), the central proteolytic machinery of mammalian cells, mainly responsible for proteostasis, as well as the “autophagy-lysosomal system”, which mediates the turnover of organelles and large aggregates.Many age-related pathologies and the aging process itself are accompanied by a dysregulation of UPS, autophagy and the cross-talk between both systems. This review will describe the sources and effects of oxidative stress, preservation of cellular protein- and organelle-homeostasis and the effects of aging on proteostasis in mammalian cells.

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“…An inducible form of the 20S proteasome (i20S), induced by cytokines such as interferon gamma (IFNɣ) and tumour necrosis factor alpha (TNFα), also exists, which is thought to be key to antigen presentation by the major histocompatibility complex (Johnston‐Carey et al . ). In common with the other proteostatic pathways, multiple components of the UPS are known to be negatively affected by ageing (Grune et al .…”

Section: Introductionmentioning

confidence: 97%

Proteostasis and ageing: insights from long‐lived mutant mice

Sands

Page

Selman

2017

The Journal of Physiology

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The global increase in life expectancy is creating significant medical, social and economic challenges to current and future generations. Consequently, there is a need to identify the fundamental mechanisms underlying the ageing process. This knowledge should help develop realistic interventions capable of combatting age‐related disease, and thus improving late‐life health and vitality. While several mechanisms have been proposed as conserved lifespan determinants, the loss of proteostasis – where proteostasis is defined here as the maintenance of the proteome – appears highly relevant to both ageing and disease. Several studies have shown that multiple proteostatic mechanisms, including the endoplasmic reticulum (ER)‐induced unfolded protein response (UPR), the ubiquitin–proteasome system (UPS) and autophagy, appear indispensable for longevity in many long‐lived invertebrate mutants. Similarly, interspecific comparisons suggest that proteostasis may be an important lifespan determinant in vertebrates. Over the last 20 years a number of long‐lived mouse mutants have been described, many of which carry single‐gene mutations within the growth‐hormone, insulin/IGF‐1 or mTOR signalling pathways. However, we still do not know how these mutations act mechanistically to increase lifespan and healthspan, and accordingly whether mechanistic commonality occurs between different mutants. Recent evidence supports the premise that the successful maintenance of the proteome during ageing may be linked to the increased lifespan and healthspan of long‐lived mouse mutants.

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The Immunoproteasome in oxidative stress, aging, and disease

Cited by 84 publications

References 129 publications

Happily (n)ever after: Aging in the context of oxidative stress, proteostasis loss and cellular senescence

Happily (n)ever after: Aging in the context of oxidative stress, proteostasis loss and cellular senescence

Proteostasis, oxidative stress and aging

Proteostasis and ageing: insights from long‐lived mutant mice

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