Increased expression of heat shock protein, transferrin, and β2-microglobulin in astrocytes during scrapie

Diedrich, J.F.; Carp, Richard I.; Haase, Ashley T.

doi:10.1006/mpat.1993.1051

Cited by 35 publications

(19 citation statements)

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“…In contrast, reactive astrocytes may account for the increased levels of ␤2 microglobulin transcripts (Fig. 2B), as indicated by immunocytochemistry in mice infected with scrapie strain 22L (16).…”

Section: Discussionmentioning

confidence: 96%

“…The histopathological modifications observed in the brain of scrapie-infected animals are associated with changes in the production of certain cytokines and increased levels of a number of enzymes and transport proteins (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). The systematic study of the molecular changes that occur in the brain of scrapie-infected animals could facilitate an understanding of the pathogenesis of TSE and in particular the interrelations between the different types of cells implicated in the disease process.…”

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confidence: 99%

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Gene Expression in Scrapie

Dandoy-Dron¹,

Guillo²,

Benboudjema³

et al. 1998

Journal of Biological Chemistry

139

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To define genes associated with or responsible for the neurodegenerative changes observed in transmissible spongiform encephalopathies, we analyzed gene expression in scrapie-infected mouse brain using "mRNA differential display." The RNA transcripts of eight genes were increased 3-8-fold in the brains of scrapie-infected animals. Five of these genes have not previously been reported to exhibit increased expression in this disease: cathepsin S, the C1q B-chain of complement, apolipoprotein D, and two previously unidentified genes denominated scrapie-responsive gene (ScRG)-1 and ScRG-2, which are preferentially expressed in brain tissue. Increased expression of the three remaining genes, ␤2 microglobulin, F4/80, and metallothionein II, has previously been reported to occur in experimental scrapie. Kinetic analysis revealed a concomitant increase in the levels of ScRG-1, cathepsin S, the C1q B-chain of complement, and ␤2 microglobulin mRNA as well as glial fibrillary acidic protein and F4/80 transcripts, markers of astrocytosis and microglial activation, respectively. In contrast, the level of ScRG-2, apolipoprotein D, and metallothionein II mRNA was only increased at the terminal stage of the disease. ScRG-1 mRNA was found to be preferentially expressed in glial cells and to code for a short protein of 47 amino acids with a strong hydrophobic N-terminal region.

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Section: Discussionmentioning

confidence: 96%

mentioning

confidence: 99%

Gene Expression in Scrapie

Dandoy-Dron¹,

Guillo²,

Benboudjema³

et al. 1998

Journal of Biological Chemistry

139

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“…Prion diseases are a family of rare progressive neurodegenerative disorders that affect both humans and animals. The “prions” are transmitted to tissue and induce abnormal folding of some specific proteins and transform them into pathogenic agents called prion proteins (PrP) [92–96]. Prions can aggregate extracellularly within the CNS to form plaques known as prion plaques, which disrupt neuronal morphology.…”

Section: Role Of Hsps In Different Neurodegenerative Diseasesmentioning

confidence: 99%

“…As a consequence several “holes” are observed in the tissue with resultant spongiform architecture due to vacuole formation in neurons. The central feature of prion diseases is the aggregation of pathologic prion proteins, such as PrP c , an abnormal isoform of the cellular prion protein [92–96]. HSP70 binds to aggregated prion proteins and mediates their degradation through the proteasome pathway [36].…”

Section: Role Of Hsps In Different Neurodegenerative Diseasesmentioning

confidence: 99%

Molecular Chaperone Dysfunction in Neurodegenerative Diseases and Effects of Curcumin

Maiti

Manna

Veleri

et al. 2014

BioMed Research International

106

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The intra- and extracellular accumulation of misfolded and aggregated amyloid proteins is a common feature in several neurodegenerative diseases, which is thought to play a major role in disease severity and progression. The principal machineries maintaining proteostasis are the ubiquitin proteasomal and lysosomal autophagy systems, where heat shock proteins play a crucial role. Many protein aggregates are degraded by the lysosomes, depending on aggregate size, peptide sequence, and degree of misfolding, while others are selectively tagged for removal by heat shock proteins and degraded by either the proteasome or phagosomes. These systems are compromised in different neurodegenerative diseases. Therefore, developing novel targets and classes of therapeutic drugs, which can reduce aggregates and maintain proteostasis in the brains of neurodegenerative models, is vital. Natural products that can modulate heat shock proteins/proteosomal pathway are considered promising for treating neurodegenerative diseases. Here we discuss the current knowledge on the role of HSPs in protein misfolding diseases and knowledge gained from animal models of Alzheimer's disease, tauopathies, and Huntington's diseases. Further, we discuss the emerging treatment regimens for these diseases using natural products, like curcumin, which can augment expression or function of heat shock proteins in the cell.

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“…In searches for a scrapie-specific nucleic acid, cDNAs have been identified that are complementary to mRNAs encoding other proteins with increased expression in prion disease (96)(97)(98). Yet none of the proteins has been found to be specific for prion disease.…”

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confidence: 99%

Prions

Prusiner

1998

Proc. Natl. Acad. Sci. U.S.A.

5,334

4,235

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Prions are unprecedented infectious pathogens that cause a group of invariably fatal neurodegenerative diseases by an entirely novel mechanism. Prion diseases may present as genetic, infectious, or sporadic disorders, all of which involve modification of the prion protein (PrP). Bovine spongiform encephalopathy (BSE), scrapie of sheep, and Creutzfeldt-Jakob disease (CJD) of humans are among the most notable prion diseases. Prions are transmissible particles that are devoid of nucleic acid and seem to be composed exclusively of a modified protein (PrP Sc ). The normal, cellular PrP (PrP C ) is converted into PrP Sc through a posttranslational process during which it acquires a high ␤-sheet content. The species of a particular prion is encoded by the sequence of the chromosomal PrP gene of the mammals in which it last replicated. In contrast to pathogens carrying a nucleic acid genome, prions appear to encipher strain-specific properties in the tertiary structure of PrP Sc . Transgenetic studies argue that PrP Sc acts as a template upon which PrP C is refolded into a nascent PrP Sc molecule through a process facilitated by another protein. Miniprions generated in transgenic mice expressing PrP, in which nearly half of the residues were deleted, exhibit unique biological properties and should facilitate structural studies of PrP Sc . While knowledge about prions has profound implications for studies of the structural plasticity of proteins, investigations of prion diseases suggest that new strategies for the prevention and treatment of these disorders may also find application in the more common degenerative diseases.

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Increased expression of heat shock protein, transferrin, and β2-microglobulin in astrocytes during scrapie

Cited by 35 publications

References 0 publications

Gene Expression in Scrapie

Gene Expression in Scrapie

Molecular Chaperone Dysfunction in Neurodegenerative Diseases and Effects of Curcumin

Prions

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