Protein shape and conformation disorders {protein conformation diseases} include Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, and frontotemporal dementia. Germline mutations cause 5 to 20% of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, fronto-temporal dementia, and prion diseases. Age is a major risk factor.
Protein-polysaccharide fragments {A-beta protein} can link hydrophobic ends to form extracellular plaques {amyloid plaque}|, create free radicals, or attract microglia. Apolipoprotein E (APOE) helps A-beta protein form plaques. APOE-4 slows A-beta protein removal. Perhaps, A-beta protein disrupts calcium regulation.
Protofibrils and then plaques can be in lungs and pancreas {cystic fibrosis}|. Sodium-ion-channel and chloride-ion-channel proteins change.
Chromosome-4-tip autosomal dominant gene can cause Huntington's chorea and related diseases {polyglutamine disease, protein}. Gene has middle cytosine-adenine-guanine repeats {CAG repeat, polyglutamine} that repeat too many times, making too many glutamine amino acids, and this causes proteins to clump. Cytosine-anything-guanine regions {CxG region, polyglutamine} have many DNA hairpins, and copies often have even longer CxG repeats. Huntington's disease and polyglutamine diseases first have many protofibrils and then plaques.
Misfolded cell-surface glycoproteins {Proteinaceous Infectious Particle} {prion}| can be in vertebrates [Prusiner, 1982].
gene
All vertebrates have protease-resistant protein (PrP) genes, whose sequence controls transmissibility.
prion protein
PrP proteins can have normal forms {cellular prion protein} (PrPC), which are in neurons. PdPSc refolds PrPC and makes clumps. PrPC can change into sticky clumps if affected by other prions, especially in B cells and brain.
amyloid
Prion proteins of size 27 to 30 kilodaltons, PrP 27-30, polymerize into amyloid fibrils. Prion-disease amyloid plaques have PrP.
radiation
Prions are more stable than anthrax spores. Irradiation does not end them.
diseases
Prion brain diseases {chronic wasting disease} (CWD) can be in sheep {scrapie}, Papua New Guinea Kore tribeswomen {kuru} {laughing sickness}, people {Creutzfeldt-Jakob disease} (CJD), and cows {spongiform encephalopathy} {bovine spongiform encephalopathy} (BSE) {mad-cow disease}. Prion diseases are sporadically infectious and can inherit.
Scrapie is in sheep and so is ovine neurodegenerative disease. Scrapie PrP has altered cellular PrP.
Chronic Wasting Disease affects deer and elk herds in west USA and Canada.
Mad Cow disease caused 1990s new-variant Creutzfeldt-Jakob disease (nvCJD) outbreak. Europe and Japan screen cattle for BSE.
Inherited CJD is 10% to 15% of human prion-disease cases. Altered cellular PrP causes human Gerstmann-Sträussler-Scheinker syndrome and familial CJD. Typical cases have no sequence changes or chemical differences between normal PrP and disease PrP, but they fold into different shapes. Proteinase K digests normal PrP completely, but aggregated disease PrP resists digestion. Disease PrP prompts normal PrP refolding into disease PrP.
Disease PrP can be protease-sensitive precursors in blood, unlike normal PrP [Safar et al., 1998].
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Date Modified: 2022.0225