Causative Links between Protein Aggregation and Oxidative Stress: A Review

Abstract

Compelling evidence supports a tight link between oxidative stress and protein aggregation processes, which are noticeably involved in the development of proteinopathies, such as Alzheimer’s disease, Parkinson’s disease, and prion disease. The literature is tremendously rich in studies that establish a functional link between both processes, revealing that oxidative stress can be either causative, or consecutive, to protein aggregation. Because oxidative stress monitoring is highly challenging and may often lead to artefactual results, cutting-edge technical tools have been developed recently in the redox field, improving the ability to measure oxidative perturbations in biological systems. This review aims at providing an update of the previously known functional links between oxidative stress and protein aggregation, thereby revisiting the long-established relationship between both processes.

Regulation of titin-based cardiac stiffness by unfolded domain oxidation (UnDOx)

“…Aggregation is often thought of as a negative consequence of protein unfolding and is associated with failing proteostasis and chaperone regulation (31). However, this is unlikely to be the case for the distal I-band titin region, because chaperones have not been found to bind to titin's distal Ig domains in vivo, whereas they do associate under stress with the proximal and middle Ig-domain segments and the N2A region of titin, protecting them from aggregation (29,32).…”

Seeding and Growth of β-Amyloid Aggregates upon Interaction with Neuronal Cell Membranes

“…Therefore, measuring the amount of intracellular biothiols generated upon interacting with pre-amyloid aggregates results in a striking way to correlate the physiological effect of cytotoxic oligomers. Generated ROS in an ensemble population of cultured cells upon addition of amyloid aggregates has commonly been reported as a measure of cellular stress and cytotoxicity [13,37,38]. However, herein, we are more interested in measuring this effect at the single-cell level.…”

Formation and characterization of crosslinks, including Tyr–Trp species, on one electron oxidation of free Tyr and Trp residues by carbonate radical anion

“…5,[8][9][10][11] In contrast to this physiological role, the formation of other disuldes and dityrosine has been associated with the etiology and development of oxidative stress-related pathological conditions and diseases. 12 These species can be generated from self-reactions of thiyl (Cys ) and tyrosyl (Tyr ) radicals (with dimerization rate constants, k, z 10 8 and 10 9 M À1 s À1 ). 9,10 Other reactions can also contribute to the formation of disuldes (e.g.…”