Seeding drug discovery: Telomeric tankyrase as a pharmacological target for the pathophysiology of high-altitude hypoxia. Issue 11 (November 2021)

• Record Type: Journal Article
• Authors: Miglani, Manjula; Pasha, Qadar; Gupta, Archana; Priyadarshini, Anjali; Pati Pandey, Ramendra; Vibhuti, Arpana
• Is Part Of: Drug discovery today. Volume 26:Issue 11(2021)
• Page Start: 2774
• Page End: 2781
• Publication Date: 2021-11
• Subjects: High altitude -- Tankyrase -- Telomere -- Telomerase -- Hypobaric hypoxia -- HAPE; Drugs -- Design -- Periodicals; Drugs -- Research -- Periodicals; 615.1
• DOI: 10.1016/j.drudis.2021.07.012
• Languages: English
• ISSNs: 1359-6446

Abstract

Graphical abstract: Highlights: Hypobaric hypoxia at high altitude is responsible for AMS, HAPE and HACE. ROS due to oxidative stress, along with UV rays at HA may lead to telomeric damage. Oxidative stress inhibits telomerase activity and promote telomere erosion. Telomeric TNKS play protective roles during telomeric damage by increasing its activity. Tankyrase are involved in various physiological events of body. Abstract: Cellular exposure to extreme environments leads to the expression of multiple proteins that participate in pathophysiological manifestations. Hypobaric hypoxia at high altitude (HA) generates reactive oxygen species (ROS) that can damage telomeres. Tankyrase (TNKS) belongs to multiple telomeric protein complexes and is actively involved in DNA damage repair. Although published research on TNKS indicates its possible role in cancer and other hypoxic diseases, its role in HA sicknesses remains elusive. Understanding the roles of telomeres, telomerase, and TNKS could ameliorate physiological issues experienced at HA. In addition, telomeric TNKS could be a potential biomarker in hypoxia-induced sicknesses or acclimatization. Thus, a new research avenue on TNKS linked to HA sickness might lead to the discovery of drugs for hypobaric hypoxia.