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Fibril structure of amyloid-ß(1-42) by cryoelectron microscopy

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Science  07 Sep 2017:
eaao2825
DOI: 10.1126/science.aao2825

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  • Neurodegenerative Diseases and Cancer: Mechanism Underlying Mutual Protection
    • Qiuyun Liu, Professor, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
    • Other Contributors:
      • Yulin Wan, Student, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
      • Yunfan Shi, Student, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
      • Hongyu Zhong, Student, Sheffield Medical School, University of Sheffield, Sheffield S10 2RX, United Kingdom
      • Meng Xing, Student, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
      • Xiaoxia Li, Researcher, School of Materials Science and Engineering, Sun Yat-Sen University, China

    It was previously reported that people with neurodegenerative diseases had lower cancer risks and vice versa (1-2). The disease risks for both neurodegenerative diseases and Cancer are age-related, as seniors may have attenuated respiratory chain for energy production and a normal Krebs cycle. A recent hypothesis attributes cancer development to local HCl buildup via the joint actions of hydrogen bond donors and acceptors and basic amino acids (3-4). The Krebs cyle builds up both organic acids and protons, and numerous organic acids have modest medium lethal doses on animals (5-6). Calcium oxalate is highly insoluble and may confer stresses to cells and implicate in age-related diseases (5-6). Compounds with similar structures to oxalate, for instance ethanol and acetic acid, can extend lifespans (7-8), perhaps via the inhibition of oxalate generation. Glyoxylate is used widely in skin-care products to remove age-related wrinkles. Calcium supplement can neutralize strong acids and reduces cancer risks (3-4). Weak acids such as organic acids might counteract strong acids to reduce tumorigenesis, and China-based vinegar factories reported few cancer cases over long periods as volatile acetic acid may antagonize HCl (3-4).
    Several risk factors for Alzheimer’s diseae (AD) possess overrepresented valine residues (9), and the 2 γ-methyl groups in valine enable hyperconjugation and van der Waals interactions with the carbonyl group, consequently enhance the secondary chemic...

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    Competing Interests: None declared.
  • Integration of divalent cations and oxalate into atomic structure of amyloid
    • Qiuyun Liu, Professor, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
    • Other Contributors:
      • Jinhuan Qi, Student, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
      • Hongyu Zhong, student, Sheffield Medical School, University of Sheffield,, Sheffield S10 2RX, United Kingdom
      • Weiwei Zhang, Student, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
      • Li Yu, Student, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China

    The paper by L. Gremer et al. (6 October, p. 116) described fibril structure of amyloid-b(1–42) obtained via cryo–electron microscopy. Although it is revealing, the mechanistic insight on the etiology of Alzheimer’s disease is not clear. Valine is overrepresented in several risk factors of the disease (1). It possesses two γ-methyl groups, which enable σ-σ hyperconjugation and robust van der Waals interactions between β-carbon and carbonyl carbon, leading to the extension of C═O bond length (2, 3) and strong secondary chemical bonding of carbonyl oxygen in valine residues. The buildup of calcium and some other divalent cations triggers the formation of highly insoluble and rigid oxalate salts or phosphate, etc., and oxalate may be over-produced from the shunt of the Krebs cycle when the respiratory chain activity is attenuated in the elderly. Compounds with similar structures to oxalate, such as ethanol and acetic acid, extend lifespans (4, 5). NMR data can provide support to hyperconjugation and electron delocalization as well as van der Waals interactions when comparisons are made among leucine, valine and isoleucine residues. Atomic structures of amyloid and other risk factors need to integrate divalent cations, oxalate, phosphate, etc., for better understanding the pathology of the age-related disorder. Some of the risk factors for Alzheimer’s disease harbor high content of basic amino acids capable of attracting anions. Amino acid residues possessing similar C═O bond...

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    Competing Interests: None declared.