The Potential Roles of Redox Enzymes in Alzheimer’s Disease: Focus on Thioredoxin

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative diseases. Increasing studies have demonstrated the critical importance for redox proteins mediating neuronal protection in models of AD. This review briefly describes some of the risk factors contributing to AD, specifically highlighting the important roles of oxidative stress in the pathology of AD. Then this article concisely introduces the dysregulation and functions of two main redox enzymes, peroxiredoxins and glutaredoxins, in AD models. This review emphasizes the neuroprotective role of the third redox enzyme thioredoxin (Trx), an important multifunctional protein regulating cellular redox status. This commentary not only summarizes the alterations of Trx expression in AD patients and models, but also reviews the potential effects and mechanisms of Trx, Trx-related molecules and Trx-inducing compounds against AD. In conclusion, Trx has a potential neuroprotection in AD and may be very promising for clinical therapy of AD in the future.

Thioredoxin-1 Promotes Mitochondrial Biogenesis Through Regulating AMPK/Sirt1/PGC1α Pathway in Alzheimer's Disease

“…In the present study, administration of exogenous rhTrx-1 inhibited the production of ROS induced by Aβ 25−35 incubation and overexpression of Trx-1 in PC12 cells suppressed Aβ 25−35 -induced apoptosis ( Figure 2 ). These findings are consistent with the previous studies involving the neuroprotective roles of Trx-1 in AD ( Jia et al., 2021 ). On the other hand, AAV-mediated Trx-1 overexpression in the hippocampus shortened the escape latency of APP/PS1 mice and restored the crossing times ( Figure 4(C)–(F) ), suggesting that specific Trx-1 overexpression ameliorated the learning and memory deficit of APP/PS1 mice.…”

“…The impairment of mitochondrial function was found in the brain tissue of both alive and post-mortem AD patients ( Kerr et al, 2017 ). The mutual enhancement between Aβ and reactive oxygen species (ROS) impaired mitochondrial function, which would promote the development of AD ( Jia et al, 2021 ). It was reported that Aβ induced the phosphorylation of dynamin-related protein 1 (Drp1) and promoted excessive mitochondrial fission, which led to neuronal apoptosis ( Kim et al, 2016 ).…”

Metabolic Profile and Pathological Alterations in the Muscle of Patients with Early-Stage Amyotrophic Lateral Sclerosis

“…Increase in the expression of SOD3 mRNA was shown in mature C2C12 myotubes submitted to oxidative stress [ 67 ], and multi “omics” data analysis suggested SOD3 as a target for therapeutic purposes in AD [ 68 ]. The glutaredoxins system plays a key role in the pathophysiology of neurodegenerative diseases, such as Friedreich’s ataxia, Parkinson’s disease and AD [ 69 , 70 , 71 ]. Regarding glutaredoxin-2, studies performed on cells showed that the glutaredoxin system could decrease mutant SOD1 aggregates [ 72 , 73 ].…”

Altered Blood and Brain Expression of Inflammation and Redox Genes in Alzheimer’s Disease, Common to APPV717I × TAUP301L Mice and Patients

“…In line with our data, increased levels of the GPX3 transcript were found in the entorhinal cortex from 36 AD patients compared to 16 controls ( Table 1 ). Moreover, thioredoxin up-regulation was shown to play a neuroprotective role in AD [ 60 ]. Nevertheless, the antioxidant defense appears to be inefficient as long as disease is persisting and progressing with age in AT mice.…”