Abstract
AbstractThe central 'risk factor' for Alzheimer's disease (AD) is age. From first principles, we construct a mathematical model of protein folding and its in vivo regulation that gives this result in a natural manner. We extend the basic approach using topological information theory methods, and examine a case history of socially-induced premature aging in the United States.
Highlights
From the very beginning of protein X-ray studies, Astbury (1935) conjectured that ‘normal’ globular proteins could have a linear state. Chiti et al (1999) suggest thatIn addition to the self-chaperoning effects described above, proteins are protected from fibrillation during the process of folding by molecular chaperones... [S]elf-complementary segments are found in almost all proteins, yet not all proteins are amyloids
The implication is that chaperoning effects have evolved to constrain self-complementary segments from interacting with each other
[P]rovided appropriate conditions are maintained over prolonged periods of time, the formation of ordered amyloid protofilaments and fibrils could be an intrinsic property of many polypeptide chains, rather than being a phenomenon limited to a very few aberrant sequences
Summary
From the very beginning of protein X-ray studies, Astbury (1935) conjectured that ‘normal’ globular proteins could have a linear state. Chiti et al (1999) suggest that. From the very beginning of protein X-ray studies, Astbury (1935) conjectured that ‘normal’ globular proteins could have a linear state. In addition to the self-chaperoning effects described above, proteins are protected from fibrillation during the process of folding by molecular chaperones... [S]elf-complementary segments are found in almost all proteins, yet not all proteins are amyloids. The implication is that chaperoning effects have evolved to constrain self-complementary segments from interacting with each other. We present a sequence of increasingly complicated models of protein folding leading to an empirical study of AD at the state level in the USA that, together, emphasize the inherent role of psychosocial stressors in the acceleration of human aging. For some proteins a delicate balance between protein folding and misfolding exists that can be tipped by changes in environment, destabilizing mutations, or even protein concentration
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