Oxidative stress and mechanisms of ochronosis in alkaptonuria

摘要: Alkaptonuria (AKU) is a rare metabolic disease due to deficient activity of the enzyme homogentisate 1,2-dioxygenase (HGD), involved in Phe and Tyr catabolism. Due such deficiency, AKU patients undergo accumulation metabolite homogentisic acid (HGA), which prone oxidation/polymerization reactions causing production melanin-like pigment. Once pigment deposited onto connective tissues (mainly joints, spine, cardiac valves), classical bluish-brown discoloration imparted, leading phenomenon known as "ochronosis", hallmark AKU. A clarification molecular mechanisms for deposition ochronotic started only recently with range vitro ex vivo human models used study HGA-induced effects. Thanks redox-proteomic analyses, it was found that HGA could induce significant oxidation number serum chondrocyte proteins. Further investigations allowed highlighting how proteome alteration, lipid peroxidation, thiol depletion, amyloid contribute oxidative stress generation protein This review briefly summarizes most recent findings on AKU, helping ochronosis potentially providing basis its pharmacological treatment. Future work should be undertaken order validate results so far obtained models.