ArticleThe Journal of biological chemistry2015
Glyceraldehyde-3-phosphate Dehydrogenase Aggregates Accelerate Amyloid-β Amyloidogenesis in Alzheimer Disease.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- A Meta-Analysis of Alzheimer's Disease Brain Transcriptomic Data.Journal of Alzheimer's disease : JAD · 2019Pooled it
- VDAC1-interacting proteins: binding site mapping and their derived peptides induce apoptosis and multifaceted cellular effects.Apoptosis : an international journal on programmed cell death · 2025Article
- Amyloid-β disrupts APP-regulated protein aggregation and dissociation from recycling endosomal membranes.The EMBO journal · 2025Article
- Pharmacological Evaluation of a Traditional Thai Polyherbal Formula for Alzheimer's Disease: Evidence from In Vitro and In Silico Studies.International journal of molecular sciences · 2025Article
- Temporal Changes in Mitochondria-Centric Excitotoxic Responses Following Severe Penetrating Traumatic Brain Injury.Biomedicines · 2025Article
- Article
- Exploring glycolytic enzymes in disease: potential biomarkers and therapeutic targets in neurodegeneration, cancer and parasitic infections.Open biology · 2025Review
- Systems pharmacology and multi-scale mechanism of Enicostema axillare bioactives in treating Alzheimer disease.Inflammopharmacology · 2024Article
- A Study on Autophagy Related Biomarkers in Alzheimer's Disease Based on Bioinformatics.Cellular and molecular neurobiology · 2023Article
- Identification of glycolytic proteins as binding partners of Bri2 BRICHOS domain.Journal of pharmaceutical and biomedical analysis · 2023Article
- Exploring the Role of Glycolytic Enzymes PFKFB3 and GAPDH in the Modulation of Aβ and Neurodegeneration and Their Potential of Therapeutic Targets in Alzheimer's Disease.Applied biochemistry and biotechnology · 2023Review
- The role of sperm-specific glyceraldehyde-3-phosphate dehydrogenase in the development of pathologies-from asthenozoospermia to carcinogenesis.Frontiers in molecular biosciences · 2023Review
- Metabolic Features of Brain Function with Relevance to Clinical Features of Alzheimer and Parkinson Diseases.Molecules (Basel, Switzerland) · 2022Review
- Extracellular protein components of amyloid plaques and their roles in Alzheimer's disease pathology.Molecular neurodegeneration · 2021Review
- Extracellular GAPDH Promotes Alzheimer Disease Progression by Enhancing Amyloid-β Aggregation and Cytotoxicity.Aging and disease · 2021Article
- Analysis of the role of Purα in the pathogenesis of Alzheimer's disease based on RNA-seq and ChIP-seq.Scientific reports · 2021Article
- The synthesis and characterization of Bri2 BRICHOS coated magnetic particles and their application to protein fishing: Identification of novel binding proteins.Journal of pharmaceutical and biomedical analysis · 2021Article
- Glycolytic Metabolism, Brain Resilience, and Alzheimer's Disease.Frontiers in neuroscience · 2021Review
- Protective Effects and Mechanisms ofBehavioural neurology · 2021Article
- The Writers, Readers, and Erasers in Redox Regulation of GAPDH.Antioxidants (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by loss of neurons and formation of pathological extracellular deposits induced by amyloid-β peptide (Aβ). Numerous studies have established Aβ amyloidogenesis as a hallmark of AD pathogenesis, particularly with respect to mitochondrial dysfunction. We have previously shown that glycolytic glyceraldehyde-3-phosphate dehydrogenase (GAPDH) forms amyloid-like aggregates upon exposure to oxidative stress and that these aggregates contribute to neuronal cell death. Here, we report that GAPDH aggregates accelerate Aβ amyloidogenesis and subsequent neuronal cell death both in vitro and in vivo. Co-incubation of Aβ40 with small amounts of GAPDH aggregates significantly enhanced Aβ40 amyloidogenesis, as assessed by in vitro thioflavin-T assays. Similarly, structural analyses using Congo red staining, circular dichroism, and atomic force microscopy revealed that GAPDH aggregates induced Aβ40 amyloidogenesis. In PC12 cells, GAPDH aggregates augmented Aβ40-induced cell death, concomitant with disruption of mitochondrial membrane potential. Furthermore, mice injected intracerebroventricularly with Aβ40 co-incubated with GAPDH aggregates exhibited Aβ40-induced pyramidal cell death and gliosis in the hippocampal CA3 region. These observations were accompanied by nuclear translocation of apoptosis-inducing factor and cytosolic release of cytochrome c from mitochondria. Finally, in the 3×Tg-AD mouse model of AD, GAPDH/Aβ co-aggregation and mitochondrial dysfunction were consistently detected in an age-dependent manner, and Aβ aggregate formation was attenuated by GAPDH siRNA treatment. Thus, this study suggests that GAPDH aggregates accelerate Aβ amyloidogenesis, subsequently leading to mitochondrial dysfunction and neuronal cell death in the pathogenesis of AD.
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