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<p>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 (Graphical abstract = Fig.&#xa0;2).</p> Graphical Abstract <p>Schematic representation of the role of 2-oxoglutarate dehydrogenase complex (OGDHC) dysfunction in amyloid-β-mediated mitochondrial fragmentation and mitophagy. In alzheimer’s disease, amyloid-β (Aβ) is overproduced, and its aggregation has been shown to inhibit OGDHC activity. This inhibition promotes drp1 translocation to mitochondria, excessive fission, and immature mitochondrial fragmentation, ultimately driving mitophagy</p> <p></p>

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The role of 2-Oxoglutarate dehydrogenase complex mitochondrial enzyme in alzheimer’s disease: a literature review and bioinformatics workflow

  • 期刊论文

  • 发表日期：

    2026年4月7日

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  • Fatemeh Sayehmiri,
  • Mohanna Parvenous,
  • Kimia Vakili,
  • Rasoul Ebrahimi,
  • Zehra Batool,
  • Narges Bazgir,
  • Kiarash Kazemi,
  • Maral Moafi,
  • Mohammad Javad Ebrahimi,
  • Mohammadreza Hajiesmaeili

摘要

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 (Graphical abstract = Fig. 2).

Graphical Abstract

Schematic representation of the role of 2-oxoglutarate dehydrogenase complex (OGDHC) dysfunction in amyloid-β-mediated mitochondrial fragmentation and mitophagy. In alzheimer’s disease, amyloid-β (Aβ) is overproduced, and its aggregation has been shown to inhibit OGDHC activity. This inhibition promotes drp1 translocation to mitochondria, excessive fission, and immature mitochondrial fragmentation, ultimately driving mitophagy