Human prion encephalopathies include Creutzfeldt–Jakob disease (CJD) (sporadic, familial, new variant, and iatrogenic), variable proteinase-sensitive prionopathy (VPSPr), Gerstmann–Sträussler–Scheinker syndrome (GSSS), fatal familial insomnia (FFI), Kuru, and PrP cerebral amyloid angiopathy. Prion encephalopathies can also affect animals (scrapie among flocks of sheep in the field, bovine spongiform encephalopathy (BSE), transmissible mink encephalopathy (TME), chronic wasting disease of mule, elk, and deer (CWD), etc.
Prion diseases are also named “transmissible spongiform encephalopathies” (TSE) as they are characterized by vacuolization of neurons and neuropil (spongiform changes) and are transmissible to other humans and/or animals.
In general, clinical signs include rapid progressive dementia leading to death within several months to up to 2 years, extrapyramidal and/or cerebellar signs, myocloni, characteristic EEG changes, and progressive hyperintensities (T2, FLAIR, DWI) in basal ganglia (putamen and caudate), thalami, and cortex.
Functions of the cellular prion protein (PrPC) which is expressed by neurons and astrocytes are manifold and include copper-binding in brain membrane fractions, protection against oxidative stress, neuroprotection, laminin receptor, synaptic transmission and plasticity, memory formation, neuronal excitability, calcium homeostasis, and glutamate receptor function among others.
Pathological Prion protein PrPSc is an abnormal, disease-associated form with increased ß-pleated sheet content and lacking nucleic acids. Conversion from PrPC to PrPSc proceeds by a seeded aggregation process. Prion strains lead to distinct versions of prion disease, which differ at the symptomatic and biochemical level. Host PRNP (prion protein) genotype (methionine and valine, M/M, V/V, M/V) influences phenotypic variability.
Typical prion encephalopathies are presented including Creutzfeldt–Jakob disease (CJD), Variant CJD, Gerstmann–Sträussler–Scheinker disease (GSS), fatal familial insomnia (FFI), and Kuru.
There is no specific treatment, and clinical outcome is lethal.
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