Redox proteomics gives insights into the role of oxidative stress in alkaptonuria.

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.