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How and why do toxic conformers of aberrant proteins accumulate during ageing?

Artikel i vetenskaplig tidskrift
Författare Rebecca Josefson
Rebecca Andersson
Thomas Nyström
Publicerad i Essays in Biochemistry
Volym 61
Nummer/häfte 3
Sidor 317-324
ISSN 0071-1365
Publiceringsår 2017
Publicerad vid Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi
Sidor 317-324
Språk en
Länkar dx.doi.org/10.1042/EBC20160085
Ämneskategorier Gerontologi, medicinsk/hälsovetenskaplig inriktning

Sammanfattning

Ageing can be defined as a gradual decline in cellular and physical functions accompanied by an increased sensitivity to the environment and risk of death. The increased risk of mortality is causally connected to a gradual, intracellular accumulation of so-called ageing factors, of which damaged and aggregated proteins are believed to be one. Such aggregated proteins also contribute to several age-related neurodegenerative disorders e.g. Alzheimer's, Parkinson's, and Huntington's diseases, highlighting the importance of protein quality control (PQC) in ageing and its associated diseases. PQC consists of two interrelated systems: the temporal control system aimed at refolding, repairing, and/or removing aberrant proteins and their aggregates and the spatial control system aimed at harnessing the potential toxicity of aberrant proteins by sequestering them at specific cellular locations. The accumulation of toxic conformers of aberrant proteins during ageing is often declared to be a consequence of an incapacitated temporal PQC system-i.e. a gradual decline in the activity of chaperones and proteases. Here, we review the current knowledge on PQC in relation to ageing and highlight that the breakdown of both temporal and spatial PQC may contribute to ageing and thus comprise potential targets for therapeutic interventions of the ageing process. © 2017 The Author(s).

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