SIRT1 and SIRT2: emerging targets in neurodegeneration.
Gizem Donmez,Tiago F. Outeiro +1 more
TLDR
The role of SIRT1 in neuronal differentiation due to the possible implications in neurodegenerative conditions is covered, and an outlook on the potential therapeutic value of Sirt1 and SIRT2 in these disorders is concluded.Abstract:
Sirtuins are NAD-dependent protein deacetylases known to have protective effects against age-related diseases such as cancer, diabetes, cardiovascular and neurodegenerative diseases. In mammals, there are seven sirtuins (SIRT1-7), which display diversity in subcellular localization and function. While SIRT1 has been extensively investigated due to its initial connection with lifespan extension and involvement in calorie restriction, important biological and therapeutic roles of other sirtuins have only recently been recognized. Here, we review the potential roles and effects of SIRT1 and SIRT2 in neurodegenerative diseases. We discuss different functions and targets of SIRT1 and SIRT2 in a variety of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's Disease (HD). We also cover the role of SIRT1 in neuronal differentiation due to the possible implications in neurodegenerative conditions, and conclude with an outlook on the potential therapeutic value of SIRT1 and SIRT2 in these disorders.read more
Citations
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Sirtuin activators and inhibitors : Promises, achievements, and challenges
TL;DR: Progress in understanding the mechanisms of Sirtuin modulation by such compounds provides a rational basis for further drug development.
Journal ArticleDOI
The glucagon-like peptide 1 (GLP) receptor as a therapeutic target in Parkinson's disease: mechanisms of action.
Dilan Athauda,Thomas Foltynie +1 more
TL;DR: The molecular mechanisms underlying the neuroprotective effects of GLP-1 analogues in the laboratory and their potential therapeutic utility with particular relevance to PD and PD dementia (PDD) are reviewed.
Journal ArticleDOI
Chemically Induced Degradation of Sirtuin 2 (Sirt2) by a Proteolysis Targeting Chimera (PROTAC) Based on Sirtuin Rearranging Ligands (SirReals)
Matthias Schiedel,Daniel Herp,Sören Hammelmann,Sören Swyter,Attila Lehotzky,Dina Robaa,Judit Oláh,Judit Ovádi,Wolfgang Sippl,Manfred Jung +9 more
TL;DR: This SirReal-based PROTAC is the first example of a probe that is able to chemically induce the degradation of an epigenetic eraser protein and can be readily adapted to alkynylated ligands of other targets.
Journal ArticleDOI
Emerging Role of Sirtuin 2 in the Regulation of Mammalian Metabolism
TL;DR: The role of SIRT2 in inflammation and oxidative stress due to the possible implications for metabolic disorders is covered, and its potential as a therapeutic target for the prevention and treatment of type 2 diabetes is considered.
Journal ArticleDOI
Longevity and skeletal muscle mass: the role of IGF signalling, the sirtuins, dietary restriction and protein intake
Adam P. Sharples,David C. Hughes,David C. Hughes,Colleen S. Deane,Colleen S. Deane,Amarjit Saini,Colin Selman,Claire E. Stewart +7 more
TL;DR: This paradox will be assessed and considered in the light of the following: the genetic knockout, overexpression and pharmacological models that induce lifespan extension versus the important role of these signalling pathways in SkM growth and adaptation.
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