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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
1997-2-7
|
| pubmed:abstractText |
Deposition of amyloid-beta protein (beta A) in brain parenchyma and vessel walls is a major pathological feature of Alzheimer's disease (AD). In prion-related encephalopathies (PRE), too, an altered form of prion protein (PrPsc) forms amyloid fibrils and accumulates in the brain. In both conditions the amyloid deposition is accompanied by nerve cell loss, whose pathogenesis and molecular basis are not understood. Neuropathological, genetic and biochemical studies indicate a central role of beta A in the AD pathogenesis. Synthetic peptides homologous to beta A and its fragments contribute to investigate the mechanisms of beta A deposit formation and the role played by beta A in AD pathogenesis. The physicochemical studies on the beta-sheet conformation and self-aggregation properties of beta A peptides indicate the conditions and the factors influencing the formation of beta A deposits. The neurotoxic activity of beta A and its fragments support the causal relationship between beta A deposits and the neuropathological events in AD. Numerous studies were performed to clarify the mechanism of neuronal death induced by exposure to beta A peptides. A similar approach has been used to investigate the role of PrPsc in PRE; in these diseases, the association between accumulation of PrPsc and neuropathology is evident and numerous data indicate that PrPsc itself might be the infectious agent responsible for disease transmission. Thus, PrP peptides were used to investigate the pathogenic role of PrPsc in PRE and the conformational change responsible for the conversion PrPc to PrPsc that makes the molecule apparently infectious. In particular, we synthesized a peptide homologous to residues 106-126, an integral part of all abnormal PrP isoforms that accumulate in the brain of subjects' PRE. This peptide is fibrillogenic, has secondary structure largely composed of beta-sheet and proteinase-resistant properties, is neurotoxic and induces astrogliosis. In this review, we summarize and compare the data obtained with beta A and PrP peptides and analyze the significance in terms of amyloidogenic proteins and neurodegeneration.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0301-0082
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
49
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
287-315
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading | |
| pubmed:year |
1996
|
| pubmed:articleTitle |
Amyloid in Alzheimer's disease and prion-related encephalopathies: studies with synthetic peptides.
|
| pubmed:affiliation |
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
|
| pubmed:publicationType |
Journal Article,
Review,
Research Support, Non-U.S. Gov't
|