TY - JOUR
T1 - Emerging roles of SIRT6 in human diseases and its modulators
AU - Liu, Gang
AU - Chen, Haiying
AU - Liu, Hua
AU - Zhang, Wenbo
AU - Zhou, Jia
N1 - Funding Information:
This study was partially supported by the Breakthrough Award W81XWH‐17‐1‐0071 (Jia Zhou) from the Department of Defense (DoD), grants EY022694 (Wenbo Zhang) and EY031054 (Hua Liu) from the National Institutes of Health. Jia Zhou is also supported by the John D. Stobo, M.D. Distinguished Chair Endowment Fund, and the John Sealy Memorial Endowment Fund at UTMB.
Publisher Copyright:
© 2020 Wiley Periodicals LLC
PY - 2021/3
Y1 - 2021/3
N2 - The biological functions of sirtuin 6 (SIRT6; e.g., deacetylation, defatty-acylation, and mono-ADP-ribosylation) play a pivotal role in regulating lifespan and several fundamental processes controlling aging such as DNA repair, gene expression, and telomeric maintenance. Over the past decades, the aberration of SIRT6 has been extensively observed in diverse life-threatening human diseases. In this comprehensive review, we summarize the critical roles of SIRT6 in the onset and progression of human diseases including cancer, inflammation, diabetes, steatohepatitis, arthritis, cardiovascular diseases, neurodegenerative diseases, viral infections, renal and corneal injuries, as well as the elucidation of the related signaling pathways. Moreover, we discuss the advances in the development of small molecule SIRT6 modulators including activators and inhibitors as well as their pharmacological profiles toward potential therapeutics for SIRT6-mediated diseases.
AB - The biological functions of sirtuin 6 (SIRT6; e.g., deacetylation, defatty-acylation, and mono-ADP-ribosylation) play a pivotal role in regulating lifespan and several fundamental processes controlling aging such as DNA repair, gene expression, and telomeric maintenance. Over the past decades, the aberration of SIRT6 has been extensively observed in diverse life-threatening human diseases. In this comprehensive review, we summarize the critical roles of SIRT6 in the onset and progression of human diseases including cancer, inflammation, diabetes, steatohepatitis, arthritis, cardiovascular diseases, neurodegenerative diseases, viral infections, renal and corneal injuries, as well as the elucidation of the related signaling pathways. Moreover, we discuss the advances in the development of small molecule SIRT6 modulators including activators and inhibitors as well as their pharmacological profiles toward potential therapeutics for SIRT6-mediated diseases.
KW - SIRT6
KW - activators
KW - deacetylation
KW - defatty-acylation
KW - human diseases
KW - inhibitors
KW - mono-ADP-ribosylation
KW - small molecule modulators
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U2 - 10.1002/med.21753
DO - 10.1002/med.21753
M3 - Review article
C2 - 33325563
AN - SCOPUS:85097564884
SN - 0198-6325
VL - 41
SP - 1089
EP - 1137
JO - Medicinal Research Reviews
JF - Medicinal Research Reviews
IS - 2
ER -