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[[http://www.uniprot.org/uniprot/PRIO_HUMAN PRIO_HUMAN]] Note=PrP is found in high quantity in the brain of humans and animals infected with neurodegenerative diseases known as transmissible spongiform encephalopathies or prion diseases, like: Creutzfeldt-Jakob disease (CJD), fatal familial insomnia (FFI), Gerstmann-Straussler disease (GSD), Huntington disease-like type 1 (HDL1) and kuru in humans; scrapie in sheep and goat; bovine spongiform encephalopathy (BSE) in cattle; transmissible mink encephalopathy (TME); chronic wasting disease (CWD) of mule deer and elk; feline spongiform encephalopathy (FSE) in cats and exotic ungulate encephalopathy (EUE) in nyala and greater kudu. The prion diseases illustrate three manifestations of CNS degeneration: (1) infectious (2) sporadic and (3) dominantly inherited forms. TME, CWD, BSE, FSE, EUE are all thought to occur after consumption of prion-infected foodstuffs.<ref>PMID:19936054</ref><ref>PMID:1671440</ref><ref>PMID:1975028</ref><ref>PMID:8461023</ref><ref>PMID:7902693</ref><ref>PMID:7906019</ref><ref>PMID:7913755</ref><ref>PMID:8909447</ref><ref>PMID:9266722</ref><ref>PMID:10790216</ref> Defects in PRNP are the cause of Creutzfeldt-Jakob disease (CJD) [MIM:[http://omim.org/entry/123400 123400]]. CJD occurs primarily as a sporadic disorder (1 per million), while 10-15% are familial. Accidental transmission of CJD to humans appears to be iatrogenic (contaminated human growth hormone (HGH), corneal transplantation, electroencephalographic electrode implantation, etc.). Epidemiologic studies have failed to implicate the ingestion of infected annimal meat in the pathogenesis of CJD in human. The triad of microscopic features that characterize the prion diseases consists of (1) spongiform degeneration of neurons, (2) severe astrocytic gliosis that often appears to be out of proportion to the degree of nerve cell loss, and (3) amyloid plaque formation. CJD is characterized by progressive dementia and myoclonic seizures, affecting adults in mid-life. Some patients present sleep disorders, abnormalities of high cortical function, cerebellar and corticospinal disturbances. The disease ends in death after a 3-12 months illness.<ref>PMID:19936054</ref><ref>PMID:1671440</ref><ref>PMID:1975028</ref><ref>PMID:8461023</ref><ref>PMID:7902693</ref><ref>PMID:7906019</ref><ref>PMID:7913755</ref><ref>PMID:8909447</ref><ref>PMID:9266722</ref><ref>PMID:10790216</ref> Defects in PRNP are the cause of fatal familial insomnia (FFI) [MIM:[http://omim.org/entry/600072 600072]]. FFI is an autosomal dominant disorder and is characterized by neuronal degeneration limited to selected thalamic nuclei and progressive insomnia.<ref>PMID:19936054</ref><ref>PMID:19927125</ref><ref>PMID:1347910</ref> Defects in PRNP are the cause of Gerstmann-Straussler disease (GSD) [MIM:[http://omim.org/entry/137440 137440]]. GSD is a heterogeneous disorder and was defined as a spinocerebellar ataxia with dementia and plaquelike deposits. GSD incidence is less than 2 per 100 million live births.<ref>PMID:19936054</ref><ref>PMID:19927125</ref><ref>PMID:10581485</ref><ref>PMID:2564168</ref><ref>PMID:1363810</ref><ref>PMID:7902972</ref><ref>PMID:7699395</ref><ref>PMID:7783876</ref><ref>PMID:8797472</ref><ref>PMID:9786248</ref><ref>PMID:11709001</ref> Defects in PRNP are the cause of Huntington disease-like type 1 (HDL1) [MIM:[http://omim.org/entry/603218 603218]]. HDL1 is an autosomal dominant, early onset neurodegenerative disorder with prominent psychiatric features.<ref>PMID:19936054</ref> Defects in PRNP are the cause of kuru (KURU) [MIM:[http://omim.org/entry/245300 245300]]. Kuru is transmitted during ritualistic cannibalism, among natives of the New Guinea highlands. Patients exhibit various movement disorders like cerebellar abnormalities, rigidity of the limbs, and clonus. Emotional lability is present, and dementia is conspicuously absent. Death usually occurs from 3 to 12 month after onset.<ref>PMID:19936054</ref> Defects in PRNP are the cause of spongiform encephalopathy with neuropsychiatric features (SENF) [MIM:[http://omim.org/entry/606688 606688]]; an autosomal dominant presenile dementia with a rapidly progressive and protracted clinical course. The dementia was characterized clinically by frontotemporal features, including early personality changes. Some patients had memory loss, several showed aggressiveness, hyperorality and verbal stereotypy, others had parkinsonian symptoms.<ref>PMID:19936054</ref>

==Function==

[[http://www.uniprot.org/uniprot/PRIO_HUMAN PRIO_HUMAN]] May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro). Association with GPC1 (via its heparan sulfate chains) targets PRNP to lipid rafts. Also provides Cu(2+) or ZN(2+) for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains (By similarity).<ref>PMID:12732622</ref><ref>PMID:19936054</ref><ref>PMID:20564047</ref>

==About this Structure==