title: Redox proteomics gives insights into the role of oxidative stress in alkaptonuria.
abstract: Alkaptonuria (AKU) is an ultra-rare metabolic disorder of the catabolic pathway of tyrosine and phenylalanine that has been poorly characterized at molecular level. As a genetic disease, AKU is present at birth, but its most severe manifestations are delayed due to the deposition of a dark-brown pigment (ochronosis) in connective tissues. The reasons for such a delayed manifestation have not been clarified yet, though several lines of evidence suggest that the metabolite accumulated in AKU sufferers (homogentisic acid) is prone to auto-oxidation and induction of oxidative stress. The clarification of the pathophysiological molecular mechanisms of AKU would allow a better understanding of the disease, help find a cure for AKU and provide a model for more common rheumatic diseases. With this aim, we have shown how proteomics and redox proteomics might successfully overcome the difficulties of studying a rare disease such as AKU and the limitations of the hitherto adopted approaches.
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, via Fiorentina 1, Università degli Studi di Siena, 53100 Siena, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Braconi
authors.forename: Lia
authors.initials: L
authors.lastname: Millucci
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ghezzi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Santucci
mesh_terms: D000474:Alkaptonuria / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D000975:Antioxidants / Q000627:therapeutic use; D050560:Homogentisate 1,2-Dioxygenase / Q000235:genetics; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D040901:Proteomics
chemical_list: D000975:Antioxidants; D050560:Homogentisate 1,2-Dioxygenase