Analysing Amyloid Development Attributes

An amyloid is a protein, or multiple of them, that becomes folded and twisted into such a shape where other proteins can aggregate to it and also end up folded. It’s quite clear these structures can keep on growing until eventually they become classed as a fibril with a diameter of at least 10 nanometres and possibly 100 nanometres. Of course proteins love their shape, it’s their defining characteristic and you can bet their chemistry starts failing as soon as they start clumping together. It’s a double jeopardy really, when it begins happening the human begins losing some protein functionality in a body region as well as the fibrils building up providing plaques that disrupt the local tissue physiology. Amyloids have been connected to over twenty diseases and many neurological conditions. Prions, which I trust the reader has some knowledge of, are a specific subset of amyloids which count as infectious.

The evidence is pretty consistent with high rates of amyloids being found in people with type 2 diabetes, rheumatoid arthritis and some forms of cataracts. People with neurological diseases such as Parkinson’s, Alzheimer’s and Huntington’s also show high amyloid levels. Cells which contain amyloid oligomers (a clever name, oligos means “few” in Greek and so an oligomer is like a short polymer with only a few monomers) die with a very high frequency and most worryingly we still don’t know what about amyloids trigger this cytotoxicity. Their intricate and well folded layers make amyloid structure irritatingly resistant to enzymes and chemicals that try and remove them but there have been some plausible suggestions for prevention and remedies.

It’s said that a journey of a thousand miles begins with a single step. There must always be a base protein that folds and then others grow off it. The current suspects are short peptides which are believed to have the property of amyloidogenesis and form locations called “hot spots” which are the centres of where the fibrils begin to grow. Also just because a peptide would form a layer to amyloid doesn’t mean it has the potential to start one. Amyloidogenic and amyloidic are synonymous terms. This study has aimed to examine the many potential hot spot models by simply doing that, looking at all of them. Using computers many different models for how the amyloid begins can be looked at for a particular scenario and a few of the more likely ones picked out.

Ultimately evidence was found  to confirm some of the standing theories about important characteristics of amyloidogenic peptides. Hydrophobicity is required as well as a tendency to form β pleated sheets. Also the flexibility of the amino acids was found to be a relevant characteristic as there is a high concentration of amino acids that lack mechanical flexibility within the amyloids. Hopefully further understanding of the aggregation and illness inducing ability of the amyloids will come in the future.

Paper links: Amyloidogenic motifs revealed by n-gram analysis


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