scholarly journals Sirtuins: The Future Insight

2013 ◽  
Vol 10 (2) ◽  
pp. 77-82 ◽  
Author(s):  
Bs Suvarna
Keyword(s):  
Small Molecules ◽  
Histone Deacetylases ◽  
Dual Function ◽  
New Class ◽  
Physiological Processes ◽  
Age Related ◽  
Regulation Of Metabolism ◽  
Lysine Deacetylases ◽  
Diabetes And Obesity

Sirtuins are evolutionary conserved NAD+ dependent acetyl-lysine deacetylases and ADP ribosyltransferases dual-function enzymes involved in the regulation of metabolism and lifespan. Sirtuins represent a promising new class of III NAD dependent histone deacetylases that regulate a number of physiological processes, originally identified in yeast. Sirtuins regulate various normal and abnormal cellular and metabolic processes, including tumorgenesis, neurodegeneration and processes associated with type 2 diabetes and obesity. Several age-related diseases such as Alzheimer’s disease and longevity have also been linked to the functions of sirtuins. Because of these associations, the identification of small molecules sirtuin modulators has been of significant interest. Kathmandu University Medical Journal | Vol.10 | No. 2 | Issue 38 | Apr – June 2012 | Page 77-82 DOI: http://dx.doi.org/10.3126/kumj.v10i2.7350

scholarly journals Role of GALNT2 on Insulin Sensitivity, Lipid Metabolism and Fat Homeostasis

2022 ◽  
Vol 23 (2) ◽  
pp. 929
Author(s):  
Alessandra Antonucci ◽  
Antonella Marucci ◽  
Vincenzo Trischitta ◽  
Rosa Di Paola
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Common Ground ◽  
Metabolic Diseases ◽  
Atherogenic Dyslipidemia ◽  
Physiological Processes ◽  
Protein Functions ◽  
Heavy Burden ◽  
Diabetes And Obesity

O-linked glycosylation, the greatest form of post-translational modifications, plays a key role in regulating the majority of physiological processes. It is, therefore, not surprising that abnormal O-linked glycosylation has been related to several human diseases. Recently, GALNT2, which encodes the GalNAc-transferase 2 involved in the first step of O-linked glycosylation, has attracted great attention as a possible player in many highly prevalent human metabolic diseases, including atherogenic dyslipidemia, type 2 diabetes and obesity, all clustered on the common ground of insulin resistance. Data available both in human and animal models point to GALNT2 as a molecule that shapes the risk of the aforementioned abnormalities affecting diverse protein functions, which eventually cause clinically distinct phenotypes (a typical example of pleiotropism). Pathways linking GALNT2 to dyslipidemia and insulin resistance have been partly identified, while those for type 2 diabetes and obesity are yet to be understood. Here, we will provide a brief overview on the present knowledge on GALNT2 function and dysfunction and propose novel insights on the complex pathogenesis of the aforementioned metabolic diseases, which all impose a heavy burden for patients, their families and the entire society.

scholarly journals Role of microRNAs in the process of metformin treating multiple diseases

2021 ◽  
Vol 1 (2) ◽  
pp. 69-78
Author(s):  
Ningning Ma ◽  
Jing Chen ◽  
Jin Ren
Keyword(s):  
Metabolic Diseases ◽  
Expression Profiles ◽  
Signal Pathways ◽  
Beneficial Effects ◽  
New Class ◽  
Disease States ◽  
Physiological Processes ◽  
Pleiotropic Properties

Abstract Metformin as the first-line treatment for type 2 diabetes mellitus has been discovered to exert beneficial effects on many diseases for nearly ten years, but its specific mechanism is still unclear. As a new class of gene expression regulators with pleiotropic properties, microRNAs (miRNAs) participate in multiple physiological processes such as cell differentiation, proliferation, survival, and metabolism, which drive them to play a regulatory role in the occurrence, development and even treatment of various diseases. A substantial body of research has found the relationship between metformin and miRNAs, in which metformin can alter the expression profiles of miRNAs in multiple disease states and on the other hand the signal pathways involving miRNAs may contribute to the pharmacological actions of metformin. This review summarizes the effects of metformin on miRNAs and their relationship in different diseases (like tumor, metabolic diseases, etc.), which should be of a great help for our better understanding of the mechanism of metformin for treating multiple diseases.

From Inhibition to Degradation: Targeting the Anti-apoptotic Protein Myeloid Cell Leukemia 1(MCL1)

2019 ◽  
Author(s):  
James Papatzimas ◽  
Evgueni Gorobets ◽  
Ranjan Maity ◽  
Mir Ishruna Muniyat ◽  
Justin L. MacCallum ◽  
...  
Keyword(s):  
Small Molecules ◽  
E3 Ligase ◽  
Myeloid Cell ◽  
Cell Leukemia ◽  
New Class ◽  
Apoptotic Protein ◽  
Family Protein ◽  
Ubiquitination Pathway

<div> <div> <div> <p>Here we show the development of heterobifunctional small molecules capable of selectively targeting MCL1 using a Proteolysis Targeting Chimera (PROTAC) methodology leading to successful degradation. We have confirmed the involvement of the E3 ligase CUL4A-DDB1 cereblon (CRBN) ubiquitination pathway, making these PROTACs a first step toward a new class of anti-apoptotic BCL-2 family protein degraders. </p> </div> </div> </div>

Conjugates of Classical DNA/RNA Binder with Nucleobase: Chemical, Biochemical and Biomedical Applications

2019 ◽  
Vol 26 (30) ◽  
pp. 5609-5624
Author(s):  
Dijana Saftić ◽  
Željka Ban ◽  
Josipa Matić ◽  
Lidija-Marija Tumirv ◽  
Ivo Piantanida
Keyword(s):  
Molecular Weight ◽  
Small Molecules ◽  
Biomedical Applications ◽  
Protein Targets ◽  
New Class ◽  
Rna Targets ◽  
Covalently Linked ◽  
Structural Aspects

: Among the most intensively studied classes of small molecules (molecular weight < 650) in biomedical research are small molecules that non-covalently bind to DNA/RNA, and another intensively studied class is nucleobase derivatives. Both classes have been intensively elaborated in many books and reviews. However, conjugates consisting of DNA/RNA binder covalently linked to nucleobase are much less studied and have not been reviewed in the last two decades. Therefore, this review summarized reports on the design of classical DNA/RNA binder – nucleobase conjugates, as well as data about their interactions with various DNA or RNA targets, and even in some cases protein targets are involved. According to these data, the most important structural aspects of selective or even specific recognition between small molecule and target are proposed, and where possible related biochemical and biomedical aspects were discussed. The general conclusion is that this, rather new class of molecules showed an amazing set of recognition tools for numerous DNA or RNA targets in the last two decades, as well as few intriguing in vitro and in vivo selectivities. Several lead research lines show promising advancements toward either novel, highly selective markers or bioactive, potentially druggable molecules.

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