Homogentisate 1,2 dioxygenase is expressed in brain: implications in alkaptonuria

Journal of Inherited Metabolic Disease
Giulia BernardiniAnnalisa Santucci

Abstract

Alkaptonuria is an ultra-rare autosomal recessive disease developed from the lack of homogentisate 1,2-dioxygenase (HGD) activity, causing an accumulation in connective tissues of homogentisic acid (HGA) and its oxidized derivatives in polymerized form. The deposition of ochronotic pigment has been so far attributed to homogentisic acid produced by the liver, circulating in the blood, and accumulating locally. In the present paper, we report the expression of HGD in the brain. Mouse and human brain tissues were positively tested for HGD gene expression by western blotting. Furthermore, HGD expression was confirmed in human neuronal cells that also revealed the presence of six HGD molecular species. Moreover, once cultured in HGA excess, human neuronal cells produced ochronotic pigment and amyloid. Our findings indicate that alkaptonuric brain cells produce the ochronotic pigment in loco and this may contribute to induction of neurological complications.

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Citations

Mar 4, 2015·Free Radical Biology & Medicine·Daniela BraconiAnnalisa Santucci
Apr 15, 2015·Journal of Inherited Metabolic Disease·Lia MillucciAnnalisa Santucci
Aug 19, 2015·Journal of Inherited Metabolic Disease·L R RanganathJ A Gallagher
Jul 28, 2016·Journal of Cellular Physiology·Michela GeminianiAnnalisa Santucci
Oct 21, 2018·Journal of Cellular Physiology·Giulia BernardiniAnnalisa Santucci
Feb 12, 2019·Journal of Inherited Metabolic Disease·Gabriella JacomelliAnnalisa Santucci
Mar 9, 2017·Calcified Tissue International·Lia MillucciAnnalisa Santucci
Jan 21, 2021·Journal of Cellular Physiology·Silvia GalderisiAnnalisa Santucci
Feb 4, 2021·International Journal of Molecular Sciences·Ottavia SpigaAnnalisa Santucci

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