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Abnormal Glucose Metabolism in Alzheimer’s Disease: Relation to Autophagy/Mitophagy and Therapeutic Approaches

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Abstract

Diminished glucose metabolism accompanies many neurodegenerative diseases including Alzheimer’s disease. An understanding of the relation of these metabolic changes to the disease will enable development of novel therapeutic strategies. Following a metabolic challenge, cells generally conserve energy to preserve viability. This requires activation of many cellular repair/regenerative processes such as mitophagy/autophagy and fusion/fission. These responses may diminish cell function in the long term. Prolonged fission induces mitophagy/autophagy which promotes repair but if prolonged progresses to mitochondrial degradation. Abnormal glucose metabolism alters protein signaling including the release of proteins from the mitochondria or migration of proteins from the cytosol to the mitochondria or nucleus. This overview provides an insight into the different mechanisms of autophagy/mitophagy and mitochondrial dynamics in response to the diminished metabolism that occurs with diseases, especially neurodegenerative diseases such as Alzheimer’s disease. The review discusses multiple aspects of mitochondrial responses including different signaling proteins and pathways of mitophagy and mitochondrial biogenesis. Improving cellular bioenergetics and mitochondrial dynamics will alter protein signaling and improve cellular/mitochondrial repair and regeneration. An understanding of these changes will suggest new therapeutic strategies.

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Acknowledgments

The work was supported by the National Institutes of Health (NIH) Grant AG14930 and the Burke Medical Research Institute. Dr. Dienel has made immense contributions to neurochemistry and has had a large impact on how I (we) view the brain’s use of glucose. His intellectual contribution to our understanding of how different cell types in the brain interact has changed the field and my own research. I am very grateful for many contributions and his friendship.

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Authors and Affiliations

  1. Brain and Mind Research Institute, Weill Cornell Medical College, Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY, 10605, USA

    Kalpita Banerjee, David E. Frank & Gary E. Gibson

  2. Department of Cellular and Molecular Pharmacology and Department of Neuroscience, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL, 60064, USA

    Soumyabrata Munshi

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  1. Kalpita Banerjee
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  2. Soumyabrata Munshi
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  3. David E. Frank
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  4. Gary E. Gibson
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Correspondence to Gary E. Gibson.

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Special Issue: In honor of Dr. Gerald Dienel.

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Banerjee, K., Munshi, S., Frank, D.E. et al. Abnormal Glucose Metabolism in Alzheimer’s Disease: Relation to Autophagy/Mitophagy and Therapeutic Approaches. Neurochem Res 40, 2557–2569 (2015). https://doi.org/10.1007/s11064-015-1631-0

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  • DOI: https://doi.org/10.1007/s11064-015-1631-0

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