Y. Mizuno et al., AN IMMUNOHISTOCHEMICAL STUDY ON ALPHA-KETOGLUTARATE DEHYDROGENASE COMPLEX IN PARKINSONS-DISEASE, Annals of neurology, 35(2), 1994, pp. 204-210
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.