The Molecular Basis for the Alzheimer’s Disease Related Decline in Key Mitochondrial Enzymes Is Unknown

We postulate that critical enzymes are modified post-translationally in Alzheimer’s disease. The focus is on the key mitochondrial enzyme alpha-ketoglutarate dehydrogenase complex (KGDHC). We isolate the protein from Alzheimer’s disease brains by both standard and novel methods and to determine post-translational modification by mass spectrometry. Defining the change will allow us to open many new areas of research. 

Nitration of KGDHC
KGDHC causes succinylation of hundreds of proteins. This can be seen in this blot of succinylation without or with inhibition of KGDHC. Inhibition of KGDHC with CESP reduces succinylation in cultured neurons.