Altered Gene Expression in Alzheimer's Disease Brain Tissue

May, Patrick C.; Johnson, Steven A.; Poirier, Judes; Lampert-Etchells, Martha; Finch, Caleb E.

doi:10.1017/s0317167100029796

Cited by 64 publications

(29 citation statements)

References 37 publications

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“…Many studies have associated apoJ with AD pathology. In particular, apoJ expression is increased in AD brain [108][109][110] and is present in amyloid plaques and vascular amyloid in AD cortex and hippocampus. [111][112][113][114] ApoJ has been shown to interact with Ab 115-117 and alter its ability to form fibrils [117][118][119] and modifies Abmediated neurotoxicity.…”

Section: Apolipoprotein J-mediated Transport Of Ab Across Bbbmentioning

confidence: 99%

Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests

et al. 2008

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Currently, the 'amyloid hypothesis' is the most widely accepted explanation for the pathogenesis of Alzheimer's disease (AD). According to this hypothesis, altered metabolism of the amyloid-b (Ab) peptide is central to the pathological cascade involved in the pathogenesis of AD. Although Ab is produced by almost every cell in the body, a physiological function for the peptide has not been determined, and the pathways by which Ab leads to cognitive dysfunction and cell death are unclear. Numerous therapeutic approaches that target the production, toxicity and removal of Ab are being developed worldwide. Although therapeutic treatment for AD may be imminent, the value and effectiveness of such treatment are largely dependent on early diagnosis of the disease. This review summarizes current knowledge of Ab clearance, transport and degradation, and evaluates the use of such information in the development of diagnostic tools. The conflicting results of plasma Ab ELISAs are discussed, as are the more promising results of Ab imaging by positron emission tomography. Current knowledge of Ab-binding proteins and Ab-degrading enzymes is analysed in the context of a potential therapy for AD. Transport across the blood-brain barrier by the receptor for advanced glycation end products and efflux via the multi-ligand lipoprotein receptor LRP-1 is also reviewed. Enhancing clearance and degradation of Ab remains an attractive therapeutic strategy, and improved understanding of Ab clearance may lead to advances in diagnostics and interventions designed to prevent or delay the onset of AD.

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Section: Apolipoprotein J-mediated Transport Of Ab Across Bbbmentioning

confidence: 99%

Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests

et al. 2008

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“…(3)). In humans with AD (Duguid et al, 1989;May et al, 1989) and Creutzfeldt Jacob disease (Duguid et al, 1989;) the levels of clusterin mRNA are increased, however, there is no associated increase in clusterin protein levels in AD CSF (Lidstrom et al, 2001) and the level of clusterin protein in CSF is decreased by 2.5 fold in Creutzfeldt Jacob disease (Piubelli et al, 2006). In addition, decreased levels of clusterin in the eye are thought to be responsible for deposition of Pseudo exfoliation (PEX) material in PEX syndrome (Zenkel et al, 2006) (again clusterin is found associated with PEX deposits).…”

Section: When Quality Control Is Compromised?mentioning

confidence: 99%

Extracellular Chaperones and Amyloids

Wilson¹,

Yerbury²,

Poon³

2008

Heat Shock Proteins and the Brain: Implications for Neurodegenerative Diseases and Neuroprotection

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The pathology of more than 40 human degenerative diseases is associated with fibrillar proteinaceous deposits called amyloid. Collectively referred to as protein deposition diseases, many of these affect the brain and the central nervous system. In many cases the amyloid deposits are extracellular and are found associated with newly identified abundant extracellular chaperones (ECs). Evidence is discussed which suggests an important regulatory role for ECs in amyloid formation and disposal in vivo. This is emerging as an exciting field. A model is presented in which it is proposed that, under normal conditions, ECs stabilize extracellular misfolded proteins by binding to them, and then guide them to specific receptors for uptake and subsequent degradation. In this scenario, EC receptors are a critical part of a quality control system which protects the brain against dangerously hydrophobic proteins/peptides. However, it also appears possible that in the presence of a high molar excess of misfolded protein, such as might occur during disease, the limited amounts of ECs available may actually exacerabate pathology. Further advances in understanding of the mechanisms that control extracellular protein folding are likely to identify new strategies for effective disease therapies. ABSTRACTThe pathology of more than 40 human degenerative diseases is associated with fibrillar proteinaceous deposits called amyloid. Collectively referred to as protein deposition diseases, many of these affect the brain and the central nervous system. In many cases the amyloid deposits are extracellular and are found associated with newly identified abundant extracellular chaperones (ECs). Evidence is discussed which suggests an important regulatory role for ECs in amyloid formation and disposal in vivo. This is emerging as an exciting field. A model is presented in which it is proposed that, under normal conditions, ECs stabilize extracellular misfolded proteins by binding to them, and then guide them to specific receptors for uptake and subsequent degradation. In this scenario, EC receptors are a critical part of a quality control system which protects the brain against dangerously hydrophobic proteins/peptides. However, it also appears possible that in the presence of a high molar excess of misfolded protein, such as might occur during disease, the limited amounts of ECs available may actually exacebate pathology. Further advances in understanding of the mechanisms that control extracellular protein folding are likely to identify new strategies for effective disease therapies.

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“…Nucleotide sequence analysis has revealed that pTB16 is homologous to several cDNA sequences cloned from various tissues in different species (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Some in vitro biological properties have been demonstrated for the encoded proteins, such as the induction of Sertoli cell or erythrocyte aggregation (24) and the inhibition or enhancement of hemolysis by the complement terminal complexes (13,25).…”

Section: Resultsmentioning

confidence: 99%

“…Its cDNA was first isolated from cultured Sertoli cells by Collard and Griswold (4). Since that time, many cloned cDNAs from different tissues in various physiological or pathological states were found to be identical to, or a species counterpart of, SGP-2 (5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Thus, clusterin (8), testosterone-repressed message 2 (TRPM-2) (9), T64 (10), glycoprotein III (11), serum protein 40,40 (12), complement cytolysis inhibitor (13), and pADHC-9 (Alzheimer disease hippocampus clone 9) (14) are all designations for equivalent clones in rodents, birds, ungulates, and humans.…”

mentioning

confidence: 99%

Human gliomas and epileptic foci express high levels of a mRNA related to rat testicular sulfated glycoprotein 2, a purported marker of cell death.

Danik

Chabot

Mercier

et al. 1991

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

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Clone pTB16 has been isolated by differential screening of a human glioma cDNA library. Northern blot analysis has shown that pTB16 expression is several times (>11-fold) higher in gliomas than in a primitive neuroectodermal tumor. This observation was supported by in situ hybridization and extended to nine other gliomas. Expression was virtually absent in adenocarcinoma cells metastasized to brain. Malignant gliomas showed stronger hybridization than benign gliomas, while blood capillaries did not show hybridization. pTB16 mRNA was also shown to be expressed in established glioma cell lines and at high levels in epileptic foci, indicating that expression of the gene may be limited to certain cell types and that its upregulation is not merely a consequence ofcellular proliferation. Nucleotide sequence analysis identified pTB16 as the human counterpart for rat testicular sulfated glycoprotein 2 (SGP-2), whose function in the reproductive system remains unknown. Although SGP-2 transcripts, and hence pTB16, were recently shown to be increased in neurodegenerative diseases such as scrapie in hamsters and Alzheimer disease in humans, our observations with brain tumors and epilepsy are suggestive of a role for pTB16 in neuropathologies in general and support the hypothesis of its involvement in tissue remodeling and cell death.

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Altered Gene Expression in Alzheimer's Disease Brain Tissue

Cited by 64 publications

References 37 publications

Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests

Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests

Extracellular Chaperones and Amyloids

Human gliomas and epileptic foci express high levels of a mRNA related to rat testicular sulfated glycoprotein 2, a purported marker of cell death.

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