Abstract
AbstractProtein folding disorders of aging like Alzheimer's and Parkinson's diseases currently present intractable medical challenges. 'Small molecule' interventions - drug treatments - often have, at best, palliative impact, failing to alter disease course. The design of individual or population level interventions will likely require a deeper understanding of protein folding and its regulation than currently provided by contemporary 'physics' or culture-bound medical magic bullet models. Here, a topological rate distortion analysis is applied to the problem of protein folding and regulation that is similar in spirit to Tlusty's (2010a) elegant exploration of the genetic code. The formalism produces large-scale, quasi-equilibrium 'resilience' states representing normal and pathological protein folding regulation under a cellular-level cognitive paradigm similar to that proposed by Atlan and Cohen (1998) for the immune system. Generalization to long times produces diffusion models of protein folding disorders in which epigenetic or life history factors determine the rate of onset of regulatory failure, in essence, a premature aging driven by familiar synergisms between disjunctions of resource allocation and need in the context of socially or physiologically toxic exposures and chronic powerlessness at individual and group scales.
Highlights
1.1 The basic conundrumAt this writing, front page articles in major news and scientific media trumpet the intractability of protein folding disorders with headlines like “No Magic Bullet Against Alzheimer’s Disease” (Kolata, 2010)
The extreme nature of American individualism suggests that a psychology based on late 20th century American research stands the risk of developing models that are particular to that culture, but of developing an understanding of the self that is peculiar in the context of the world’s cultures
Kim and Hecht (2006) suggest that overall amyloid fibril geometry is very much driven by the underlying β-sheet coding 1010101, the rate of fibril formation may be determined by exact chemical constitution
Summary
Front page articles in major news and scientific media trumpet the intractability of protein folding disorders with headlines like “No Magic Bullet Against Alzheimer’s Disease” (Kolata, 2010). Qiu et al (2009) explain that mutation effects account for only a small fraction of observed cases, and that the APOE 4 allele – the only established genetic factor for both early and late onset disease – is a susceptibility gene, neither necessary nor sufficient for disease onset They further describe how many of the same factors implicated in diabetes and cardiovascular disease predict onset of Alzheimer’s as well: tobacco use, high blood pressure, high serum cholesterol, chronic inflammation, as indexed by a higher level of serum C-reactive protein, and diabetes itself. Qui et al conclude: Epidemiological research has provided sufficient evidence that vascular risk factors in middle-aged and older adults play a significant role in the develolpment and progression of dementia and [Alzheimer’s disease], whereas extensive social network and active engagement in mental, social, and physical activities may postpone the onset of the dementing disorder. We will take what Heine and colleagues might describe as an ‘East Asian’ approach to protein folding disorders, and examine their embedding context from a new perspective, as opposed to perceiving them as separated from their backcloth, and ‘naturally’ amenable to magic bullets
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