Exploring aldose reductase inhibitors as promising therapeutic targets for diabetes-linked disabilities

Int J Biol Macromol. 2024 Nov;280(Pt 2):135761. doi: 10.1016/j.ijbiomac.2024.135761. Epub 2024 Sep 19.

Abstract

Diabetes mellitus significantly increases mortality and morbidity rates due to complications like neuropathy and nephropathy. It also leads to retinopathy and cataract formation, which is a leading cause of vision disability. The polyol pathway emerges as a promising therapeutic target among the various pathways associated with diabetic complications. This review focuses on the development of natural and synthetic aldose reductase inhibitors (ARIs), along with recent discoveries in diabetic complication treatment. AR, pivotal in the polyol pathway converting glucose to sorbitol, plays a key role in secondary diabetes complications' pathophysiology. Understanding AR's function and structure lays the groundwork for improving ARIs to mitigate diabetic complications. New developments in ARIs open up exciting possibilities for treating diabetes-related complications. However, it is still challenging to get preclinical successes to clinical effectiveness because of things like differences in how the disease starts, drug specificity, and the complexity of the AR's structure. Addressing these challenges is crucial for developing targeted and efficient ARIs. Continued research into AR's structural features and specific ARIs is essential. Overcoming these challenges could revolutionize diabetic complication treatment, enhance patient outcomes, and reduce the global burden of diabetes-related mortality and morbidity.

Keywords: Aldose reductase inhibitor; Diabetic complications; Diabetic retinopathy.

Publication types

  • Review

MeSH terms

  • Aldehyde Reductase* / antagonists & inhibitors
  • Aldehyde Reductase* / metabolism
  • Animals
  • Diabetes Complications* / drug therapy
  • Diabetes Mellitus / drug therapy
  • Enzyme Inhibitors* / chemistry
  • Enzyme Inhibitors* / pharmacology
  • Enzyme Inhibitors* / therapeutic use
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use

Substances

  • Aldehyde Reductase
  • Enzyme Inhibitors
  • Hypoglycemic Agents