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The central region (residues 6195), also known as the NAC domain, can form cross -sheets and consists of a highly hydrophobic sequence underlying its high propensity for aggregation and leading to protofibril and fibril formation (Uda et al., 1993

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doi: 10.1016/j.urology.2011.10.013 25 SesterhennIADavisCJ

Some of the resulting organic acids are thought to bear a direct toxicity to mitochondria, which leads to dysfunction of high energy-demanding organs such as the heart, the optic nerve, the liver, the brain, and the hematological precursor cells

PMC 6848746

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