Aldose reductase (AR) is the rate-limiting step in the polyol pathway, where it converts glucose into sorbitol [1]. The activation of the polyol pathway occurs when an excess of glucose is present in the system, leading to the generation of fructose, akin to glycolysis. Hyperglycemia leads to the activation of the polyol pathway, which can further have detrimental effects on cells and tissues due to NADH/NAD + redox imbalance. The accumulation of sorbitol within cells leads to osmotic stress and cellular damage, activating advanced glycation end products (AGEs), and reactive oxidative species (ROS). Activating protein kinase C (PKC), which can contribute to inflammation and tissue damage in various diseases [2].

AR's involvement in inflammatory responses is due to its role in elevating ROS. Numerous studies have focused on inhibiting AR and assessing its downstream impact on cells to determine if AR is an attractive therapeutic target to prevent cell damage [1,3]. AR inhibition has been shown to mitigate Sirt1-mediated inflammation [4], NF-κB pathway activation [5], NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated innate immune response [6] along with various other inflammatory markers [7]. AR inhibitors can prevent inflammation by preventing ROS levels from increasing, thereby blocking inflammatory pathways triggered by ROS.

Central nervous system (CNS) degenerative diseases are complex processes, involving various inflammatory mediators and cellular responses, resulting in irreversible damage. Understanding the mechanisms underlying inflammatory response in these conditions is essential to develop effective therapeutic strategies. Given AR's ability to reduce these markers, this review delves into the connection between AR and inflammation in CNS related neurodegeneration. We highlight the significance of AR, an inflammatory response mediator, in modulating this neuroinflammation. Furthermore, we also discuss the role of AR in peripheral nervous system (PNS) related neurodegeneration.