Immunoreactive Levels of α-ketoglutarate Dehydrogenase Subunits in Friedreich's Ataxia and Spinocerebellar Ataxia Type 1

• Published in: Neurodegeneration (London, England) Vol. 5; no. 1; pp. 27 - 33
• Main Authors: Mastrogiacomo, Frank, LaMarche, Jacques, Dožić, Slobodan, Lindsay, Gordon, Bettendorff, Lucien, Robitaille, Yves, Schut, Lawrence, Kish, Stephen J.
• Format: Journal Article Web Resource
• Language: English
• Published: England Elsevier Ltd 01.03.1996; Academic Press
• Subjects: Acyltransferases - analysis; Adult; Analysis of Variance; Biochemistry, biophysics & molecular biology; Biochimie, biophysique & biologie moléculaire; Brain - enzymology; Brain - pathology; Cerebellar Cortex - enzymology; cerebellum; Friedreich Ataxia - enzymology; Friedreich's ataxia; Frontal Lobe - enzymology; Humans; Ketoglutarate Dehydrogenase Complex - analysis; Ketoglutarate Dehydrogenase Complex - metabolism; Life sciences; Macromolecular Substances; Occipital Lobe - enzymology; olivopontocerebellar atrophy; Postmortem Changes; Reference Values; Sciences du vivant; spinocerebellar ataxia type 1; Spinocerebellar Degenerations - enzymology; Thiamine; Time Factors; α-ketaglutarate dehydrogenase complex; α-ketaglutarate dehydrogenase complex; Friedreich's ataxia; olivopontocerebellar atrophy; spinocerebellar ataxia type 1; cerebellum
• ISSN: 1055-8330; 1522-9661
• DOI: 10.1006/neur.1996.0004

Enzyme activities of α-ketoglutarate dehydrogenase complex (αKGDHC) and one of its constituent subunits, dihydrolipoamide dehydrogenase (E3), are reported to be reduced in non-CNS tissues of some patients with Friedreich's ataxia (FA); however, the results are highly confliicting. To determine whether an enzyme abnormality occurs in brain, we measured immunoreactive levels of the three αKGDHC subunits, namely, α-ketoglutarate dehydrogenase (E1), dihydro-lipoamide succinyltransferase (E2) and E3 in postmortem frontal, occipital and cerebellar cortices of 18 control subjects, 9 patients with FA and, for comparison, 12 patients with spinocerebellar ataxia type 1 (SCA1). Decreased (−20 to −31%) levels of E3 were observed in all three examined areas of the patients with FA with the changes statistically significant in cerebellar and frontal cortices. The E3 reduction could be explained by a loss of αKGDHC or other dehydrogenase complexes (e.g. pyruvate dehydrogenase complex) which utilize this subunit. In SCA1, enzyme changes were limited to E2 in cerebellar (−26%) and frontal (−19%) cortices. Although the E3 and E2 reductions are only slight, and may represent secondary events, the changes in this key Krebs cycle enzyme could exacerbate degenerative processes in both of the spinocerebellar ataxia disorders.