Upregulation of N-acetylaspartic acid resulting nitric oxide toxicity induces aspartoacylase mutations and protein interaction to cause pathophysiology seen in Canavan disease.

[canavan disease]

Aspartoacylase (ASPA ) converts N-acetylaspartic acid into aspartate and acetate . In Canavan disease (CD ), N-acetylaspartic acid (NAA ) is found to be increased and over 65 mutations including IVS 4 +1 G → T , deletion of introns and exons have been reported in the ASPA gene . These changes lead to severe form or mild form of CD . The present study was aimed to understand mechanism in the cause of mutations in ASPA and pathophysiology seen in patients with CD . We have reported that elevated levels of NAA induce inducible nitric oxide (iNOS ) to produce nitric oxide toxicity in CD . Nitric oxide toxicity has been shown to induce several mutations including base change G → T and deletion and enhances protein interaction in several genes . Therefore we hypothesize that upregulation of NAA stimulates NOS and the resulting nitric oxide toxicity induces ASPA mutations and protein interaction to result pathophysiological abnormalities seen in patients with CD .

Diseases
Validation

Diseases presenting "severe form" symptom

alpha-thalassemia

benign recurrent intrahepatic cholestasis

canavan disease

child syndrome

congenital adrenal hyperplasia

dentinogenesis imperfecta

dystrophic epidermolysis bullosa

fabry disease

familial hypocalciuric hypercalcemia

familial mediterranean fever

harlequin ichthyosis

heparin-induced thrombocytopenia

hirschsprung disease

inclusion body myositis

kindler syndrome

lamellar ichthyosis

legionellosis

locked-in syndrome

megacystis-microcolon-intestinal hypoperistalsis syndrome

neonatal adrenoleukodystrophy

neuralgic amyotrophy

papillon-lefèvre syndrome

zellweger syndrome

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