Are advanced glycation end-product-modified proteins of pathogenetic importance in fibromyalgia?

Abstract

AGE modification of proteins leads to reduced solubility and high resistance to proteolytic digestion of such altered proteins (e.g. AGE-modified collagens). AGEs are also able to stimulate different kinds of cells via activation of the NFkappaB, mediated by specific receptors of AGEs (e.g. RAGE) on the cell surface. Both mechanisms may contribute to the development, perpetuation and spreading of pain phenomena in FM patients.

Cross‐Linking in Collagen by Nonenzymatic Glycation Increases the Matrix Stiffness in Rabbit Achilles Tendon

“…Nonenzymatic glycation of the tissue proteins and subsequent production of AGEs have been implicated in the process of normal aging as well as in the pathogenesis of several diseases, including diabetes [1,3], atherosclerosis [8], fibromyalgia [9], uremia [10,11], Alzheimer's disease [12,13], and renal failure [14]. Compared to other tissues, connective tissue appears to be highly vulnerable to glycation in the body.…”

“…These Amadori products are believed to undergo a series of reactions to form heterogeneous complex fluorophores and chromophores collectively referred to as advanced Maillard products or advanced glycation end products (AGEs). The production of these AGE products have been implicated in the etiology of the long-term complications of several human afflictions, such as diabetes [1,3,6], aging [7], atherosclerosis [8], fibromyalgia [9], uremia [10,11], Alzheimer's disease [12,13], and renal failure [14].…”

Detection of elevated Nε‐carboxymethyllysine levels in muscular tissue and in serum of patients with fibromyalgia

“…AGEs accumulated in vivo are involved in the process of ageing and in the pathogenesis of various diseases (3). We previously reported significantly elevated pentosidine levels, another AGE structure, in patients with FM (5).…”

Fibromyalgia: Mechanisms, Current Treatment and Animal Models

“…RAGE is reportedly upregulated in the peripheral and central nervous systems of mice following streptozotocin-induced diabetic neuropathy [40]. Similarly, changes in expression of RAGE in peripheral tissues have been reported in human disease [41,42]. RAGE receptors are elevated in FMS patients, and as such may represent a novel drug target for FMS [41,42].…”

“…Similarly, changes in expression of RAGE in peripheral tissues have been reported in human disease [41,42]. RAGE receptors are elevated in FMS patients, and as such may represent a novel drug target for FMS [41,42]. Serum levels of N -carboxymethyllysine (CML); a ligand for RAGE, were significantly elevated in a study of 14 FMS patients and 3 healthy controls [42].…”