The Role of 2-Oxoglutarate Dehydrogenase Complex Mitochondrial Enzyme in Alzheimer’S Disease: A Literature Review and Bioinformatics Workflow Publisher Pubmed



Sayehmiri F ; Parvenous M ; Vakili K ; Ebrahimi R ; Batool Z ; Bazgir N ; Kazemi K ; Moafi M ; Ebrahimi MJ ; Hajiesmaeili M
Source: Metabolic Brain Disease Published:2026

Abstract

Alzheimer’s disease (AD) is a leading neurodegenerative disorder and a significant cause of senile dementia. While the exact mechanisms of AD remain unclear, key hypotheses include the accumulation of amyloid-β (Aβ) plaques and hyperphosphorylated Tau tangles in the hippocampus and cortex. Recent evidence highlights the significant role of damaged mitochondria in AD pathogenesis. Abnormal glucose metabolism contributes to neurodegeneration by affecting enzymes in the tricarboxylic acid (TCA) cycle, particularly the mitochondrial 2-oxoglutarate dehydrogenase (OGDHC) complex, which is vital for the oxidative decarboxylation of 2-oxoglutarate. Impaired OGDHC function is associated with energy failure, oxidative stress, neuroinflammation, and calcium irregularities, all of which may worsen AD progression. This study reviews the evidence linking mitochondrial dysfunction to AD, emphasizing OGDHC deficiency. Additionally, we conducted a bioinformatics analysis to identify key genes in mitochondrial metabolic pathways, highlighting the critical role of OGDHC in AD-related mitochondrial dysfunction ( © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2026.