AN IMMUNOHISTOCHEMICAL STUDY ON ALPHA-KETOGLUTARATE DEHYDROGENASE COMPLEX IN PARKINSONS-DISEASE

We report an immunohistochemical study of the mitochondrial a-ketoglut arate dehydrogenase complex (KGDHC) in the substantia nigra in Parkins on's disease. The KGDHC, the three enzyme complex catalyzing the oxida tion of alpha-ketoglutarate to succinate through succinic semialdehyde , is the rate-regulating enzyme of the TCA cycle. The mitochondrial to xin, MPP(+), inhibits not only complex I but also the KGDHC. Therefore , we investigated this enzyme complex in Parkinson's disease. In the c ontrol patients (n = 6), the immunostaining of the melanized nigral ne urons was generally uniform; most of the melanized neurons showed good immunostaining with Some neurons showing somewhat reduced staining. I n Parkinson's disease (n = 9), many melanized neurons showed reduced i mmunostaining for the KGDHC, and those neurons were more frequently se en in the lateral one-third of substantia nigra. The decrease in the i mmunostaining for the KGDHC correlated roughly with the severity of de generation. The KGDHC is more vulnerable to degeneration than complex Ii, III, and IV as noted in our previous immunohistochemical study. Ev en if secondary, the loss may play a role in the progression of the di sease.