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McCully KS. Hyperhomocysteinemia, Suppressed Immunity, and Altered Oxidative Metabolism Caused by Pathogenic Microbes in Atherosclerosis and Dementia. Front Aging Neurosci. 2017;9:324doi: 10.3389/fnagi.2017.00324.
McCully, K. S. (2017). Hyperhomocysteinemia, Suppressed Immunity, and Altered Oxidative Metabolism Caused by Pathogenic Microbes in Atherosclerosis and Dementia. Frontiers in aging neuroscience, 9324. https://doi.org/10.3389/fnagi.2017.00324
McCully, Kilmer S. "Hyperhomocysteinemia, Suppressed Immunity, and Altered Oxidative Metabolism Caused by Pathogenic Microbes in Atherosclerosis and Dementia." Frontiers in aging neuroscience vol. 9 (2017): 324. doi: https://doi.org/10.3389/fnagi.2017.00324
McCully KS. Hyperhomocysteinemia, Suppressed Immunity, and Altered Oxidative Metabolism Caused by Pathogenic Microbes in Atherosclerosis and Dementia. Front Aging Neurosci. 2017 Oct 06;9:324. doi: 10.3389/fnagi.2017.00324. eCollection 2017. PMID: 29056905; PMCID: PMC5635055.
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Front Aging Neurosci. 2017 Oct 06;9:324. doi: 10.3389/fnagi.2017.00324. eCollection 2017.

Hyperhomocysteinemia, Suppressed Immunity, and Altered Oxidative Metabolism Caused by Pathogenic Microbes in Atherosclerosis and Dementia.

Frontiers in aging neuroscience

Kilmer S McCully

Affiliations

  1. Pathology, VA Boston Healthcare System (VHA), Boston, MA, United States.
  2. Pathology, Harvard Medical School, Boston, MA, United States.

PMID: 29056905 PMCID: PMC5635055 DOI: 10.3389/fnagi.2017.00324

Abstract

Many pathogenic microorganisms have been demonstrated in atherosclerotic plaques and in cerebral plaques in dementia. Hyperhomocysteinemia, which is a risk factor for atherosclerosis and dementia, is caused by dysregulation of methionine metabolism secondary to deficiency of the allosteric regulator, adenosyl methionine. Deficiency of adenosyl methionine results from increased polyamine biosynthesis by infected host cells, causing increased activity of ornithine decarboxylase, decreased nitric oxide and peroxynitrate formation and impaired immune reactions. The down-regulation of oxidative phosphorylation that is observed in aging and dementia is attributed to deficiency of thioretinaco ozonide oxygen complexed with nicotinamide adenine dinucleotide and phosphate, which catalyzes oxidative phosphorylation. Adenosyl methionine biosynthesis is dependent upon thioretinaco ozonide and adenosine triphosphate (ATP), and the deficiency of adenosyl methionine and impaired immune function in aging are attributed to depletion of thioretinaco ozonide from mitochondrial membranes. Allyl sulfides and furanonaphthoquinones protect against oxidative stress and apoptosis by increasing the endogenous production of hydrogen sulfide and by inhibiting electron transfer to the active site of oxidative phosphorylation. Diallyl trisulfide and napabucasin inhibit the signaling by the signal transducer and activator of transcription 3 (Stat3), potentially enhancing immune function by effects on T helper lymphocytes and promotion of apoptosis. Homocysteine promotes endothelial dysfunction and apoptosis by the unfolded protein response and endoplasmic reticulum stress through activation of the N-methyl D-aspartate (NMDA) receptor, causing oxidative stress, calcium influx, apoptosis and endothelial dysfunction. The prevention of atherosclerosis and dementia may be accomplished by a proposed nutritional metabolic homocysteine-lowering protocol which enhances immunity and corrects the altered oxidative metabolism in atherosclerosis and dementia.

Keywords: allylsulfides; atherosclerosis; dementia; furanonaphthoquinones; homocysteine; oxidation; thioretinaco ozonide

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