Premium
Homogentisate 1,2 dioxygenase is expressed in brain: implications in alkaptonuria
Author(s) -
Bernardini Giulia,
Laschi Marcella,
Geminiani Michela,
Braconi Daniela,
Vannuccini Elisa,
Lupetti Pietro,
Manetti Fabrizio,
Millucci Lia,
Santucci Annalisa
Publication year - 2015
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-015-9829-5
Subject(s) - alkaptonuria , homogentisic acid , ochronosis , chorea , blot , human brain , microbiology and biotechnology , biology , biochemistry , chemistry , gene , pathology , medicine , disease , neuroscience
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.