title: Homogentisate 1,2 dioxygenase is expressed in brain: implications in alkaptonuria.
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.
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, and Dipartimento di Scienze della Vita, Università degli Studi di Siena, via Aldo Moro 2, 53100, Siena, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Bernardini
authors.forename: Marcella
authors.initials: M
authors.lastname: Laschi
authors.forename: Michela
authors.initials: M
authors.lastname: Geminiani
authors.forename: Daniela
authors.initials: D
authors.lastname: Braconi
authors.forename: Elisa
authors.initials: E
authors.lastname: Vannuccini
authors.forename: Pietro
authors.initials: P
authors.lastname: Lupetti
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Manetti
authors.forename: Lia
authors.initials: L
authors.lastname: Millucci
authors.forename: Annalisa
authors.initials: A
authors.lastname: Santucci
mesh_terms: D000474:Alkaptonuria / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D050560:Homogentisate 1,2-Dioxygenase / Q000378:metabolism*; D006713:Homogentisic Acid / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D009794:Ochronosis / Q000378:metabolism / Q000473:pathology
chemical_list: D050560:Homogentisate 1,2-Dioxygenase; D006713:Homogentisic Acid