ArticleJournal of pharmaceutical analysis2023
PKM2-mediated neuronal hyperglycolysis enhances the risk of Parkinson's disease in diabetic rats.
Article in Journal of pharmaceutical analysis, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Enhanced Glycolysis-Driven Histone H3K18 Lactylation Regulates Epileptogenesis by Modulating the E3 Ubiquitin Ligase COP1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Shikonin alleviates rotenone-induced Parkinson's disease neuroinflammation by targeting PKM2-mediated glycolytic MG-Hs production.Cell communication and signaling : CCS · 2025Article
- Gastrodin inhibits hexokinase-2 mediated glycolysis to rescue rotenone-damaged PC12 cells.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Neuroprotective effects of semaglutide and metformin against rotenone-induced neurobehavioral changes in male diabetic rats.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- YOD1 regulates oxidative damage of dopamine neurons in Parkinson's disease by deubiquitinating PKM2.Clinical and translational medicine · 2025Article
- Glucose Metabolic Reprogramming in Microglia: Implications for Neurodegenerative Diseases and Targeted Therapy.Molecular neurobiology · 2025Review
- Hyperglycemia Aggravates 6-Hydroxydopamine-Induced Neuronal Ferroptosis via SLC7A11-Dependent Pathway in Diabetic PD Rat Model.CNS neuroscience & therapeutics · 2025Article
- The role of PKM2-mediated metabolic reprogramming in the osteogenic differentiation of BMSCs under diabetic periodontitis conditions.Stem cell research & therapy · 2025Article
- PKM2-mediated metabolic reprogramming of microglia in neuroinflammation.Cell death discovery · 2025Review
- Exploring glycolytic enzymes in disease: potential biomarkers and therapeutic targets in neurodegeneration, cancer and parasitic infections.Open biology · 2025Review
- Proteomic Identification of ALDOA as a Pathogenic TDP-43 Interaction Partner in ALS.Degenerative neurological and neuromuscular disease · 2025Article
- A crazy trio in Parkinson's disease: metabolism alteration, α-synuclein aggregation, and oxidative stress.Molecular and cellular biochemistry · 2025Review
- The Role of PKM2 in Multiple Signaling Pathways Related to Neurological Diseases.Molecular neurobiology · 2024Review
- Fluorescent immunoassay for chloramphenicol based on the label-free polyadenine-mediated spherical nucleic acids triggered signal amplification.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2024Article
- Inhibition of Pyruvate kinase M2 (PKM2) by shikonin attenuates isoproterenol-induced acute myocardial infarction via reduction in inflammation, hypoxia, apoptosis, and fibrosis.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Ginsenoside Rk3 is a novel PI3K/AKT-targeting therapeutics agent that regulates autophagy and apoptosis in hepatocellular carcinoma.Journal of pharmaceutical analysis · 2023Article
- Uncovering novel therapeutic targets in glucose, nucleotides and lipids metabolism during cancer and neurological diseases.International journal of immunopathology and pharmacologyReview
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epidemiological and animal studies indicate that pre-existing diabetes increases the risk of Parkinson's disease (PD). However, the mechanisms underlying this association remain unclear. In the present study, we found that high glucose (HG) levels in the cerebrospinal fluid (CSF) of diabetic rats might enhance the effect of a subthreshold dose of the neurotoxin 6-hydroxydopamine (6-OHDA) on the development of motor disorders, and the damage to the nigrostriatal dopaminergic neuronal pathway. In vitro, HG promoted the 6-OHDA-induced apoptosis in PC12 cells differentiated to neurons with nerve growth factor (NGF) (NGF-PC12). Metabolomics showed that HG promoted hyperglycolysis in neurons and impaired tricarboxylic acid cycle (TCA cycle) activity, which was closely related to abnormal mitochondrial fusion, thus resulting in mitochondrial loss. Interestingly, HG-induced upregulation of pyruvate kinase M2 (PKM2) combined with 6-OHDA exposure not only mediated glycolysis but also promoted abnormal mitochondrial fusion by upregulating the expression of MFN2 in NGF-PC12 cells. In addition, we found that PKM2 knockdown rescued the abnormal mitochondrial fusion and cell apoptosis induced by HG+6-OHDA. Furthermore, we found that shikonin (SK), an inhibitor of PKM2, restored the mitochondrial number, promoted TCA cycle activity, reversed hyperglycolysis, enhanced the tolerance of cultured neurons to 6-OHDA, and reduced the risk of PD in diabetic rats. Overall, our results indicate that diabetes promotes hyperglycolysis and abnormal mitochondrial fusion in neurons through the upregulation of PKM2, leading to an increase in the vulnerability of dopaminergic neurons to 6-OHDA. Thus, the inhibition of PKM2 and restoration of mitochondrial metabolic homeostasis/pathways may prevent the occurrence and development of diabetic PD.
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