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dc.contributor.author
Van Vickle, Gregory D.
dc.contributor.author
Esh, Chera L.
dc.contributor.author
Kokjohn, Tyler A.
dc.contributor.author
Patton, R. Lyle
dc.contributor.author
Kalback, Walter M.
dc.contributor.author
Luehrs, Dean C.
dc.contributor.author
Beach, Thomas G.
dc.contributor.author
Newel, Amanda J.
dc.contributor.author
Lopera, Francisco
dc.contributor.author
Ghetti, Bernardino
dc.contributor.author
Vidal, Rubén Alejandro
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dc.contributor.author
Castaño, Eduardo Miguel
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dc.contributor.author
Roher, Alex E.
dc.date.available
2017-08-18T19:30:42Z
dc.date.issued
2008-03
dc.identifier.citation
Van Vickle, Gregory D.; Esh, Chera L.; Kokjohn, Tyler A.; Patton, R. Lyle; Kalback, Walter M.; et al.; Presenilin-1 280Glu-->Ala mutation alters C-terminal APP processing yielding longer abeta peptides: implications for Alzheimer's disease; Feinstein Institute for Medical Research; Molecular Medicine; 14; 3-4; 3-2008; 184-194
dc.identifier.issn
1076-1551
dc.identifier.uri
http://hdl.handle.net/11336/22687
dc.description.abstract
Presenilin (PS) mutations enhance the production of the Abeta42 peptide that is derived from the amyloid precursor protein (APP). The pathway(s) by which the Abeta42 species is preferentially produced has not been elucidated, nor is the mechanism by which PS mutations produce early-onset dementia established. Using a combination of histological, immunohistochemical, biochemical, and mass spectrometric methods, we examined the structural and morphological nature of the amyloid species produced in a patient expressing the PS1 280Glu-->Ala familial Alzheimer's disease mutation. Abundant diffuse plaques were observed that exhibited a staining pattern and morphology distinct from previously described PS cases, as well as discreet amyloid plaques within the white matter. In addition to finding increased amounts of CT99 and Abeta42 peptides, our investigation revealed the presence of a complex array of Abeta peptides substantially longer than 42/43 amino acid residue species. The increased hydrophobic nature of longer Abeta species retained within the membrane walls could impact the structure and function of plasma membrane and organelles. These C-terminally longer peptides may, through steric effects, dampen the rate of turnover by critical amyloid degrading enzymes such as neprilysin and insulin degrading enzyme. A complete understanding of the deleterious side effects of membrane bound Abeta as a consequence of gamma-secretase alterations is needed to understand Alzheimer's disease pathophysiology and will aid in the design of therapeutic interventions.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Feinstein Institute for Medical Research
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Presenilin
dc.subject
Mutations
dc.subject
Transgenic Mice
dc.subject.classification
Bioquímica y Biología Molecular
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Presenilin-1 280Glu-->Ala mutation alters C-terminal APP processing yielding longer abeta peptides: implications for Alzheimer's disease
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-07-18T14:50:22Z
dc.identifier.eissn
1528-3658
dc.journal.volume
14
dc.journal.number
3-4
dc.journal.pagination
184-194
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
Nueva York
dc.description.fil
Fil: Van Vickle, Gregory D.. Sun Health Research Institute; Estados Unidos
dc.description.fil
Fil: Esh, Chera L.. Sun Health Research Institute; Estados Unidos
dc.description.fil
Fil: Kokjohn, Tyler A.. Sun Health Research Institute; Estados Unidos
dc.description.fil
Fil: Patton, R. Lyle. Sun Health Research Institute; Estados Unidos
dc.description.fil
Fil: Kalback, Walter M.. Sun Health Research Institute; Estados Unidos
dc.description.fil
Fil: Luehrs, Dean C.. Sun Health Research Institute; Estados Unidos
dc.description.fil
Fil: Beach, Thomas G.. Sun Health Research Institute; Estados Unidos
dc.description.fil
Fil: Newel, Amanda J.. Sun Health Research Institute; Estados Unidos
dc.description.fil
Fil: Lopera, Francisco. Universidad de Antioquía; Colombia
dc.description.fil
Fil: Ghetti, Bernardino. Indiana University; Estados Unidos
dc.description.fil
Fil: Vidal, Rubén Alejandro. Indiana University; Estados Unidos
dc.description.fil
Fil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
dc.description.fil
Fil: Roher, Alex E.. Sun Health Research Institute; Estados Unidos
dc.journal.title
Molecular Medicine
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2258166/
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