Abstract::AGEs are molecules formed by nonenzymatic glycation of proteins, lipids,
and nucleic acids, a process accelerated under hyperglycemic conditions such as DM1.
These molecules interact with specific receptors, particularly the Receptor for AGEs
(RAGE), triggering intracellular signaling cascades that promote oxidative stress
through the generation of Reactive Oxygen Species (ROS) and activation of inflammatory
pathways. A critical pathological mechanism involves the formation of neoantigens,
modified self-proteins that elicit immune responses. Structural alterations caused by
AGEs expose new epitopes or modify existing ones, making them targets for autoreactive
T cells and autoantibodies. This mechanism is implicated in autoimmune skin diseases
such as vitiligo and bullous pemphigoid. Oxidative stress plays a central role in these
diseases, exacerbated by AGEs through the generation of ROS and depletion of antioxidants,
leading to melanocyte destruction in vitiligo and tissue damage in bullous
pemphigoid. In addition, hypoxia enhances ROS production, mitochondria, and other
cellular systems contributing to oxidative stress. Emerging evidence suggests that hypoxia
can be mitigated by oxygen nanobubbles. Targeting AGE formation and oxidative
stress presents a promising approach for the management of autoimmune skin disorders
in DM1. Therapeutic strategies targeting AGE formation, oxidative stress, and immune
dysregulation show promise for managing autoimmune skin disorders in Type 1 Diabetes
Mellitus (T1DM). AGE inhibitors, such as aminoguanidine and pyridoxamine, reduce
non-enzymatic protein glycation, limiting AGE accumulation and inflammatory
signaling. Antioxidants, including polyphenols, vitamins C and E, N-acetylcysteine, selenium,
and hydrogen-rich water, help neutralize Reactive Oxygen Species (ROS), restoring
oxidative balance. Combining AGE inhibitors and antioxidants may provide synergistic
benefits by reducing oxidative stress and protein immunogenicity. Additionally,
immune modulation therapies, such as Treg therapy and cytokine inhibitors, aim to restore
immune tolerance and prevent autoimmune activation. Anti-TNF-α and IL-6 inhibitors
offer targeted inflammation suppression, while RAGE antagonists mitigate AGE-induced
immune dysregulation. This study aims to explore the role of Advanced Glycation
End products (AGEs) in the pathogenesis of autoimmune skin disorders associated
with type 1 Diabetes Mellitus (DM1) and to evaluate potential therapeutic strategies targeting
AGE formation and oxidative stress.