High glycine content in TDP-43: a potential culprit in limbic-predominant age-related TDP-43 encephalopathy.

The Journal of International Medical Research
Shanshan AnQiuyun Liu

Abstract

Numerous risk factors for heart disease or dementia harbor over 10% valine plus glycine content. Interestingly, TDP-43 contains 6.0% valine and 13.3% glycine, and the buildup of this protein in the brains of patients with limbic-predominant age-related TDP-43 encephalopathy has dire consequences. The two γ-methyl groups in valine enable hyperconjugation, which enhances the van der Waals interaction between its side group and the carbonyl carbon. This extends the C=O bond length, and this weakened C=O bond augments the secondary chemical bonding of the carbonyl oxygen atom to cations. This, in turn, promotes the formation and buildup of insoluble and rigid salts such as calcium oxalate, which is postulated to be a major cause of heart disease. Similarly, the long C=O bond length in glycine results in a weakened C=O bond with an enhanced affinity toward cations and the formation of insoluble salts. Further, several prion proteins possess a high glycine content of approximately 20%. The insoluble calcium salts produced may promote aggregate formation via secondary chemical bonding between calcium and glycine, as well as between calcium and valine. Chemical and biochemical insights will help us to better understand the etiology of ...Continue Reading

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Feb 1, 2018·European Journal of Preventive Cardiology·Ran HeQiuyun Liu
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Mar 24, 2018·European Journal of Preventive Cardiology·Tao GanQiuyun Liu
Dec 30, 2018·Medical Hypotheses·Shanshan AnQiuyun Liu
Mar 22, 2019·European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (ECP)·Yulin WanQiuyun Liu
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Citations

Sep 22, 2020·Cancer Control : Journal of the Moffitt Cancer Center·Shanshan AnQiuyun Liu
Jan 11, 2022·ACS Chemical Neuroscience·Xiaoxiao ZhangQiuyun Liu

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