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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

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Abstract

Alzheimer’s disease (AD) is presently the 6th major cause of mortality across the globe. However, it is expected to rise rapidly, following cancer and heart disease, as a leading cause of death among the elderly peoples. AD is largely characterized by metabolic changes linked to glucose metabolism and age-induced mitochondrial failure. Recent research suggests that the glycolytic pathway is required for a range of neuronal functions in the brain including synaptic transmission, energy production, and redox balance; however, alteration in glycolytic pathways may play a significant role in the development of AD. Moreover, it is hypothesized that targeting the key enzymes involved in glucose metabolism may help to prevent or reduce the risk of neurodegenerative disorders. One of the major pro-glycolytic enzyme is 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3); it is normally absent in neurons but abundant in astrocytes. Similarly, another key of glycolysis is glyceraldehyde-3-phosphate dehydrogenase (GAPDH) which catalyzes the conversion of aldolase and glyceraldehyde 3 phosphates to 1,3 bisphosphoglycerate. GAPDH has been reported to interact with various neurodegenerative disease–associated proteins, including the amyloid-β protein precursor (AβPP). These findings indicate PFKFB3 and GAPDH as a promising therapeutic target to AD. Current review highlight the contributions of PFKFB3 and GAPDH in the modulation of Aβand AD pathogenesis and further explore the potential of PFKFB3 and GAPDH as therapeutic targets in AD.

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Funding

This work was supported by the fund from Department of Health Research, New Delhi, India (File No. R.12014/61/2020-HR) to IA.

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  1. Imran Ahmad and Saurabh Pal contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry, King George’s Medical University, Lucknow, 226003, Uttar Pradesh, India

    Imran Ahmad, Ranjana Singh, Soni Prajapati & Yusra Laiq

  2. Department of Biotechnology, Era’s Lucknow Medical College & Hospital, Era University, Lucknow, 226003, Uttar Pradesh, India

    Saurabh Pal

  3. Cell and Neurobiology Laboratory, Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India

    Nidhi Sachan

  4. Department of Zoology, University of Lucknow, Lucknow, 226007, Uttar Pradesh, India

    Hadiya Husain

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  1. Imran Ahmad
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  2. Ranjana Singh
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Contributions

IA and RS conceived the idea and designed the review structure. IA, SP, YL, SP, and HH wrote the first draft of the manuscript. All authors discussed, critically reviewed the manuscript, and approved the final version for submission.

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Correspondence to Imran Ahmad or Ranjana Singh.

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Ahmad, I., Singh, R., Pal, S. et al. 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. Appl Biochem Biotechnol 195, 4673–4688 (2023). https://doi.org/10.1007/s12010-023-04340-0

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