Opportunities for Therapeutic Modulation of O-GlcNAc DOI

Steven S. Cheng,

Alison Mody,

Christina M. Woo

и другие.

Chemical Reviews, Год журнала: 2024, Номер 124(22), С. 12918 - 13019

Опубликована: Ноя. 7, 2024

O-Linked β-N-acetylglucosamine (O-GlcNAc) is an essential, dynamic monosaccharide post-translational modification (PTM) found on serine and threonine residues of thousands nucleocytoplasmic proteins. The installation removal O-GlcNAc controlled by a single pair enzymes, transferase (OGT) O-GlcNAcase (OGA), respectively. Since its discovery four decades ago, has been diverse classes proteins, playing important functional roles in many cellular processes. Dysregulation homeostasis implicated the pathogenesis disease, including neurodegeneration, X-linked intellectual disability (XLID), cancer, diabetes, immunological disorders. These foundational studies disease biology have motivated efforts to target therapeutically, with multiple clinical candidates under evaluation. In this review, we describe characterization biochemistry OGT OGA, regulation, development OGA inhibitors, pathophysiology, progress modulators, emerging opportunities for targeting O-GlcNAc. This comprehensive resource should motivate further study into function inspire strategies therapeutic modulation

Язык: Английский

Type 2 Diabetes Mellitus: A Comprehensive Review of Pathophysiology, Comorbidities, and Emerging Therapies DOI
Aditi Singh,

Sucharita Shadangi,

Pulkit Kr. Gupta

и другие.

Comprehensive physiology, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 1, 2025

ABSTRACT Humans are perhaps evolutionarily engineered to get deeply addicted sugar, as it not only provides energy but also helps in storing fats, which survival during starvation. Additionally, sugars (glucose and fructose) stimulate the feel‐good factor, they trigger secretion of serotonin dopamine brain, associated with reward sensation, uplifting mood general. However, when consumed excess, contributes imbalance, weight gain, obesity, leading onset a complex metabolic disorder, generally referred diabetes. Type 2 diabetes mellitus (T2DM) is one most prevalent forms diabetes, nearly affecting all age groups. T2DM clinically diagnosed cardinal sign chronic hyperglycemia (excessive sugar blood). Chronic hyperglycemia, coupled dysfunctions pancreatic β‐cells, insulin resistance, immune inflammation, further exacerbate pathology T2DM. Uncontrolled T2DM, major public health concern, significantly toward progression several micro‐ macrovascular diseases, such diabetic retinopathy, nephropathy, neuropathy, atherosclerosis, cardiovascular including cancer. The current review discusses epidemiology, causative factors, pathophysiology, comorbidities, existing emerging therapies related It future roadmap for alternative drug discovery management

Язык: Английский

Процитировано

1

Opportunities for Therapeutic Modulation of O-GlcNAc DOI

Steven S. Cheng,

Alison Mody,

Christina M. Woo

и другие.

Chemical Reviews, Год журнала: 2024, Номер 124(22), С. 12918 - 13019

Опубликована: Ноя. 7, 2024

O-Linked β-N-acetylglucosamine (O-GlcNAc) is an essential, dynamic monosaccharide post-translational modification (PTM) found on serine and threonine residues of thousands nucleocytoplasmic proteins. The installation removal O-GlcNAc controlled by a single pair enzymes, transferase (OGT) O-GlcNAcase (OGA), respectively. Since its discovery four decades ago, has been diverse classes proteins, playing important functional roles in many cellular processes. Dysregulation homeostasis implicated the pathogenesis disease, including neurodegeneration, X-linked intellectual disability (XLID), cancer, diabetes, immunological disorders. These foundational studies disease biology have motivated efforts to target therapeutically, with multiple clinical candidates under evaluation. In this review, we describe characterization biochemistry OGT OGA, regulation, development OGA inhibitors, pathophysiology, progress modulators, emerging opportunities for targeting O-GlcNAc. This comprehensive resource should motivate further study into function inspire strategies therapeutic modulation

Язык: Английский

Процитировано

1