Biomaterial Database

Neuroprotective and neurotoxic signaling by the prion protein. 2011

Ulrike K Resenberger, and Konstanze F Winklhofer, and Jörg Tatzelt

Neurobiochemistry, Adolf-Butenandt-Institute, Ludwig-Maximilians-University Munich, Munich, Germany.

Prion diseases in humans and animals are characterized by progressive neurodegeneration and the formation of infectious particles called prions. Both features are intimately linked to a conformational transition of the cellular prion protein (PrP(C)) into aberrantly folded conformers with neurotoxic and self-replicating activities. Interestingly, there is increasing evidence that the infectious and neurotoxic properties of PrP conformers are not necessarily coupled. Transgenic mouse models revealed that some PrP mutants interfere with neuronal function in the absence of infectious prions. Vice versa, propagation of prions can occur without causing neurotoxicity. Consequently, it appears plausible that two partially independent pathways exist, one pathway leading to the propagation of infectious prions and another one that mediates neurotoxic signaling. In this review we will summarize current knowledge of neurotoxic PrP conformers and discuss the role of PrP(C) as a mediator of both stress-protective and neurotoxic signaling cascades.

UI	MeSH Term	Description	Entries
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D011328	Prions	Small proteinaceous infectious particles which resist inactivation by procedures that modify NUCLEIC ACIDS and contain an abnormal isoform of a cellular protein which is a major and necessary component. The abnormal (scrapie) isoform is PrPSc (PRPSC PROTEINS) and the cellular isoform PrPC (PRPC PROTEINS). The primary amino acid sequence of the two isoforms is identical. Human diseases caused by prions include CREUTZFELDT-JAKOB SYNDROME; GERSTMANN-STRAUSSLER SYNDROME; and INSOMNIA, FATAL FAMILIAL.	Mink Encephalopathy Virus,Prion,Encephalopathy Virus, Mink
D011487	Protein Conformation	The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).	Conformation, Protein,Conformations, Protein,Protein Conformations
D011489	Protein Denaturation	Disruption of the non-covalent bonds and/or disulfide bonds responsible for maintaining the three-dimensional shape and activity of the native protein.	Denaturation, Protein,Denaturations, Protein,Protein Denaturations
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D015398	Signal Transduction	The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.	Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D017096	Prion Diseases	A group of genetic, infectious, or sporadic degenerative human and animal nervous system disorders associated with abnormal PRIONS. These diseases are characterized by conversion of the normal prion protein to an abnormal configuration via a post-translational process. In humans, these conditions generally feature DEMENTIA; ATAXIA; and a fatal outcome. Pathologic features include a spongiform encephalopathy without evidence of inflammation. The older literature occasionally refers to these as unconventional SLOW VIRUS DISEASES. (From Proc Natl Acad Sci USA 1998 Nov 10;95(23):13363-83)	Dementias, Transmissible,Spongiform Encephalopathies, Transmissible,Transmissible Dementias,Encephalopathies, Spongiform, Transmissible,Human Transmissible Spongiform Encephalopathies, Inherited,Inherited Human Transmissible Spongiform Encephalopathies,Prion Disease,Prion Protein Diseases,Prion-Associated Disorders,Prion-Induced Disorder,Prion-Induced Disorders,Transmissible Spongiform Encephalopathies,Dementia, Transmissible,Disorder, Prion-Induced,Disorders, Prion-Induced,Encephalopathies, Transmissible Spongiform,Encephalopathy, Transmissible Spongiform,Prion Induced Disorder,Prion Protein Disease,Spongiform Encephalopathy, Transmissible,Transmissible Dementia,Transmissible Spongiform Encephalopathy