Role of Thioredoxin System in Regulating Cellular Redox Status in Alzheimer’s Disease

Issue title: Pro-Oxidants and Antioxidants in Alzheimer’s Disease

Guest editors: Pravat K. Mandal

Article type: Review Article

Authors: Qaiser, Hammad^a | Uzair, Mohammad^a | Al-Regaiey, Khalid^b | Rafiq, Shafia^a | Arshad, Muhammad^a | Yoo, Woo-Kyoung^c | Arain, Osama Zahid^d | Kaleem, Imdad^e | Abualait, Turki^f | Wang, Lan^{g; h} | Wang, Ran^{g; h} | Bashir, Shahid^{d; *}

Affiliations: [a] Department of Biological Sciences, Faculty of Basic & Applied Sciences, International Islamic University Islamabad, Pakistan | [b] Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia | [c] Department of Physical Medicine and Rehabilitation, Hallym University College of Medicine, Anyang, Gyeonggi-do, Republic of Korea | [d] Neuroscience Center, King Fahad Specialist Hospital, Dammam, Saudi Arabia | [e] Department of Biosciences, COMSATS University, Islamabad, Pakistan | [f] College of Applied Medical Sciences, Imam Abdulrahman Bin Faisal University, Dammam, Eastern Province, Saudi Arabia | [g] Department of Psychiatry, The First Hospital of Hebei Medical University, Shijiazhuang, China | [h] Mental Health Institute of Hebei Medical University, Shijiazhuang, China

Correspondence: [*] Correspondence to: Shahid Bashir, King Fahad Specialist Hospital, Neuroscience Center, Ammar Bin Thabit Street, Dammam – 31444, Saudi Arabia. E-mail: [email protected].

Abstract: Alzheimer’s disease (AD) is the most common form of dementia and a public health problem. It exhibits significant oxidative stress and redox alterations. The antioxidant enzyme systems defend the cellular environment from oxidative stress. One of the redox systems is the thioredoxin system (TS), which exerts decisive control over the cellular redox environment. We aimed to review the protective effects of TS, which include thioredoxin (Trx), thioredoxin reductase (TrxR), and NADPH. In the following, we discussed the physiological functioning and the role of the TS in maintaining the cellular redox-homeostasis in the AD-damaged brain. Trx protects the cellular environment from oxidative stress, while TrxR is crucial for the cellular detoxification of reactive oxygen species in the brain. However, TS dysregulation increases the susceptibility to cellular death. The changes in Trx and TrxR levels are significantly associated with AD progression. Though the data from human, animal, and cellular models support the neuroprotective role of TS in the brain of AD patients, the translational potential of these findings to clinical settings is not yet applied. This review summarizes the current knowledge on the emerging role of the TrxR-Trx system in AD.

Keywords: Alzheimer’s disease, antioxidant enzymes, oxidative stress, reactive oxygen species, redox enzymes, thioredoxin, thioredoxin reductase

DOI: 10.3233/JAD-230394

Journal: Journal of Alzheimer's Disease, vol. 99, no. s1, pp. S97-S108, 2024