Ageing is a major risk factor for the development of many diseases, prominently including neurodegenerative disorders such as Alzheimer disease and Parkinson disease. A hallmark of many age-related diseases is the dysfunction in protein homeostasis (proteostasis), leading to the accumulation of protein aggregates. In healthy cells, a complex proteostasis network, comprising molecular chaperones and proteolytic machineries and their regulators, operates to ensure the maintenance of proteostasis. These factors coordinate protein synthesis with polypeptide folding, the conservation of protein conformation and protein degradation. However, sustaining proteome balance is a challenging task in the face of various external and endogenous stresses that accumulate during ageing. These stresses lead to the decline of proteostasis network capacity and proteome integrity. The resulting accumulation of misfolded and aggregated proteins affects, in particular, postmitotic cell types such as neurons, manifesting in disease. Recent analyses of proteome-wide changes that occur during ageing inform strategies to improve proteostasis. The possibilities of pharmacological augmentation of the capacity of proteostasis networks hold great promise for delaying the onset of age-related pathologies associated with proteome deterioration and for extending healthspan.
Cellular stress induced by the abnormal accumulation of unfolded or misfolded proteins at the endoplasmic reticulum (ER) is emerging as a possible driver of human diseases, incl...
The unfolded protein response (UPR) allows the endoplasmic reticulum (ER) to recover from the accumulation of misfolded proteins, in part by increasing its folding capacity. Ino...
In this study, we show a correlation between synthesis of aberrant proteins and their oxidative modification. The level of aberrant proteins was elevated in Escherichia coli cul...
The unfolded protein response (UPR) is an intracellular signaling pathway that is activated by the accumulation of unfolded proteins in the endoplasmic reticulum (ER). UPR activ...
A wide variety of neurodegenerative diseases are characterized by the accumulation of intracellular or extracellular protein aggregates. More recently, the genetic identificatio...
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