The hallmark of these progressive neurodegenerative diseases is the accumulation of the protease-resistant, pathologic conformation of prion protein (PrPres) in the CNS.
These thalamic abnormalities have not been fully evaluated to date, and detecting them might be useful for differentiating GSS102 from other neurodegenerative disorders.
Mutations in the prion protein gene (PRNP) were first found to be causal of IPD in 1989, before the molecular genetic characterisation of any other neurodegenerative disease.
Gerstmann-Sträussler-Scheinker disease (GSS) is an inherited neurodegenerative disorder associated with mutations in the prion protein gene and accumulation of misfolded PrP with protease-resistant fragments (PrP(res)) of 6-8 kDa.
Aggregation and misfolding of the prion protein (PrP) are thought to be the cause of a family of lethal neurodegenerative diseases affecting humans and other animals.
Because PrP(C) serves as the substrate for Creutzfeldt-Jakob Disease (CJD), these data suggest mechanistic similarities between the two neurodegenerative diseases.
The presence of pathology related to the deposition of amyloid-β (Aβ) has been recently reported in iatrogenic Creutzfeldt-Jakob disease (iCJD) acquired from inoculation of growth hormone (GH) extracted from human cadaveric pituitary gland or use of cadaveric dura mater (DM) grafts.To investigate this phenomenon further, a cohort of 27 iCJD cases - 21 with adequate number of histopathological sections - originating from Australia, France, Italy, and the Unites States, were examined by immunohistochemistry, amyloid staining, and Western blot analysis of the scrapie prion protein (PrP<sup>Sc</sup>), and compared with age-group matched cases of sporadic CJD (sCJD), Alzheimer disease (AD) or free ofneurodegenerative diseases (non-ND).Cases of iCJD and sCJD shared similar profiles of proteinase K-resistant PrP<sup>Sc</sup> with the exception of iCJD harboring the "MMi" phenotype.
Finally, we discuss the recently identified sheddase of PrP(C), namely the metalloprotease ADAM10, with regard to therapeutic potential against neurodegenerative diseases.
This fatal neurodegenerative disease is caused by misfolding of the cellular prion protein to pathogenic β-rich conformers (PrPSc) that accumulate in higher order structures of the brain and other tissues.
Prion diseases are neurodegenerative disorders characterized by the accumulation of an abnormal isoform of the protease-insensitive isoform (PrPSc) of prion protein.
Prion diseases are fatal neurodegenerative disorders associated with the deposition of abnormal prion protein aggregates (PrP<sup>Sc</sup>) in the brain tissue.
Prion diseases are a group of neurodegenerative disorders associated with conversion of a normal prion protein, PrPC, into a pathogenic conformation, PrPSc.
This review highlights some important metabolic alterations detected in neurodegeneration caused by misfolded prion protein and discusses common toxicity pathways identified across different neurodegenerative diseases.
An increasing body of evidence indicates that the canonical mechanism of conformational corruption of cellular prion protein (PrP<sup>C</sup>) by the pathogenic isoform (PrP<sup>Sc</sup>) that is the basis of prion formation in TSEs is common to a spectrum of proteins associated with various additional human neurodegenerative disorders, including the more common Alzheimer's and Parkinson's diseases.
Polymorphisms of the prion protein gene (PRNP) are known to cause a strong susceptibility to the occurrence of prion diseases, such as Creutzfeldt-Jakob disease, and might be associated with other neurodegenerative disorders.
In this manuscript, we review the data supporting a role for PrP(C) at the intersection of different neurodegenerative diseases, discuss potential mechanisms by which this protein could mediate neurotoxic signals, and examine therapeutic approaches that may arise from the identification of PrP(C)-directed compounds.
The prion protein (PrP<sup>C</sup>) can be structurally shifted to its PrP<sup>Sc</sup> isoform causing a wide range of neurodegenerative diseases, which are currently incurable.
Prion diseases or transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases where the misfolding of the prion protein (PrP) is a crucial event.
The discovery that prion protein can misfold into a pathological conformation that encodes structural information capable of both propagation and inducing severe neuropathology has revolutionized our understanding of neurodegenerative disease.
GSS is defined as a neurodegenerative disease "in family with dominantly inherited progressive ataxia and/or dementia): encephalo(myelo)pathy with multi-centric PrP plaques".