ArticleNeurobiology of aging2012
Deficits in the mitochondrial enzyme α-ketoglutarate dehydrogenase lead to Alzheimer's disease-like calcium dysregulation.
Article in Neurobiology of aging, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 69 citations in OpenAlex.
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- Myelin Lipid Reserves as a Conditional Metabolic Buffer: Implications for Alzheimer's Disease and Ischemic Stroke.Neuromolecular medicine · 2026Review
- Impairment of Tricarboxylic Acid Cycle (TCA) Cycle in Alzheimer's Disease: Mechanisms, Implications, and Potential Therapies.Aging and disease · 2025Review
- Neurologic Deficit Score at 4-5 Days Post-eCPR Predicts Long-Term Brain Dysfunction in Rats Following Cardiac Arrest.Biomolecules · 2025Article
- A scoping review regarding reproductive capacity modulation based on alpha-ketoglutarate supplementation.Reproduction (Cambridge, England) · 2024Article
- Research Progress on the Pathogenesis, Diagnosis, and Drug Therapy of Alzheimer's Disease.Brain sciences · 2024Review
- Parapyruvate Induces Neurodegeneration in C57BL/6JNarl Mice via Inhibition of the α-Ketoglutarate Dehydrogenase Complex.ACS omega · 2024Article
- Identification of key lipid metabolism-related genes in Alzheimer's disease.Lipids in health and disease · 2023Article
- Transcriptomic Analyses of Neurotoxic Astrocytes Derived from Adult Triple Transgenic Alzheimer's Disease Mice.Journal of molecular neuroscience : MN · 2023Article
- Phytochemicals: A Promising Alternative for the Prevention of Alzheimer's Disease.Life (Basel, Switzerland) · 2023Review
- β-Glucans in particulate and solubilized forms elicit varied immunomodulatory and apoptosis effects in teleost macrophages in a dosedependent manner.Frontiers in immunology · 2023Article
- The α-Ketoglutarate Dehydrogenase Complex as a Hub of Plasticity in Neurodegeneration and Regeneration.International journal of molecular sciences · 2022Review
- Altered Metabolism in Alzheimer Disease Brain: Role of Oxidative Stress.Antioxidants & redox signaling · 2022Review
- Exploring Sex-Related Differences in Microglia May Be a Game-Changer in Precision Medicine.Frontiers in aging neuroscience · 2022Review
- Suppression of a core metabolic enzyme dihydrolipoamide dehydrogenase (Genes & diseases · 2021Article
- Molecular Mechanism of Arsenic-Induced Neurotoxicity including Neuronal Dysfunctions.International journal of molecular sciences · 2021Review
- Review
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- Selective linkage of mitochondrial enzymes to intracellular calcium stores differs between human-induced pluripotent stem cells, neural stem cells, and neurons.Journal of neurochemistry · 2021Article
- Mitochondria-associated membranes (MAMs): a potential therapeutic target for treating Alzheimer's disease.Clinical science (London, England : 1979) · 2021Review
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Understanding the molecular sequence of events that culminate in multiple abnormalities in brains from patients that died with Alzheimer's disease (AD) will help to reveal the mechanisms of the disease and identify upstream events as therapeutic targets. The activity of the mitochondrial α-ketoglutarate dehydrogenase complex (KGDHC) in homogenates from autopsy brain declines with AD. Experimental reductions in KGDHC in mouse models of AD promote plaque and tangle formation, the hallmark pathologies of AD. We hypothesize that deficits in KGDHC also lead to the abnormalities in endoplasmic reticulum (ER) calcium stores and cytosolic calcium following K(+) depolarization that occurs in cells from AD patients and transgenic models of AD. The activity of the mitochondrial enzyme KGDHC was diminished acutely (minutes), long-term (days), or chronically (weeks). Acute inhibition of KGDHC produced effects on calcium opposite to those in AD, while the chronic or long-term inhibition of KGDHC mimicked the AD-related changes in calcium. Divergent changes in proteins released from the mitochondria that affect endoplasmic reticulum calcium channels may underlie the selective cellular consequences of acute versus longer term inhibition of KGDHC. The results suggest that the mitochondrial abnormalities in AD can be upstream of those in calcium.
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Registered trials
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