Cargando…
Transmembrane Amyloid-Related Proteins in CSF as Potential Biomarkers for Alzheimer’s Disease
In the continuing search for new cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease (AD), reasonable candidates are the secretase enzymes involved in the processing of the amyloid precursor protein (APP), as well as the large proteolytic cleavage fragments sAPPα and sAPPβ. The enzymatic ac...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451586/ https://www.ncbi.nlm.nih.gov/pubmed/26082753 http://dx.doi.org/10.3389/fneur.2015.00125 |
_version_ | 1782374160703422464 |
---|---|
author | Lopez-Font, Inmaculada Cuchillo-Ibañez, Inmaculada Sogorb-Esteve, Aitana García-Ayllón, María-Salud Sáez-Valero, Javier |
author_facet | Lopez-Font, Inmaculada Cuchillo-Ibañez, Inmaculada Sogorb-Esteve, Aitana García-Ayllón, María-Salud Sáez-Valero, Javier |
author_sort | Lopez-Font, Inmaculada |
collection | PubMed |
description | In the continuing search for new cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease (AD), reasonable candidates are the secretase enzymes involved in the processing of the amyloid precursor protein (APP), as well as the large proteolytic cleavage fragments sAPPα and sAPPβ. The enzymatic activities of some of these secretases, such as BACE1 and TACE, have been investigated as potential AD biomarkers, and it has been assumed that these activities present in human CSF result from the soluble truncated forms of the membrane-bound enzymes. However, we and others recently identified soluble forms of BACE1 and APP in CSF containing the intracellular domains, as well as the multi-pass transmembrane presenilin-1 (PS1) and other subunits of γ-secretase. We also review recent findings that suggest that most of these soluble transmembrane proteins could display self-association properties based on hydrophobic and/or ionic interactions leading to the formation of heteromeric complexes. The oligomerization state of these potential new biomarkers needs to be taken into consideration for assessing their real potential as CSF biomarkers for AD by adequate molecular tools. |
format | Online Article Text |
id | pubmed-4451586 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-44515862015-06-16 Transmembrane Amyloid-Related Proteins in CSF as Potential Biomarkers for Alzheimer’s Disease Lopez-Font, Inmaculada Cuchillo-Ibañez, Inmaculada Sogorb-Esteve, Aitana García-Ayllón, María-Salud Sáez-Valero, Javier Front Neurol Neuroscience In the continuing search for new cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease (AD), reasonable candidates are the secretase enzymes involved in the processing of the amyloid precursor protein (APP), as well as the large proteolytic cleavage fragments sAPPα and sAPPβ. The enzymatic activities of some of these secretases, such as BACE1 and TACE, have been investigated as potential AD biomarkers, and it has been assumed that these activities present in human CSF result from the soluble truncated forms of the membrane-bound enzymes. However, we and others recently identified soluble forms of BACE1 and APP in CSF containing the intracellular domains, as well as the multi-pass transmembrane presenilin-1 (PS1) and other subunits of γ-secretase. We also review recent findings that suggest that most of these soluble transmembrane proteins could display self-association properties based on hydrophobic and/or ionic interactions leading to the formation of heteromeric complexes. The oligomerization state of these potential new biomarkers needs to be taken into consideration for assessing their real potential as CSF biomarkers for AD by adequate molecular tools. Frontiers Media S.A. 2015-06-02 /pmc/articles/PMC4451586/ /pubmed/26082753 http://dx.doi.org/10.3389/fneur.2015.00125 Text en Copyright © 2015 Lopez-Font, Cuchillo-Ibañez, Sogorb-Esteve, García-Ayllón and Sáez-Valero. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Lopez-Font, Inmaculada Cuchillo-Ibañez, Inmaculada Sogorb-Esteve, Aitana García-Ayllón, María-Salud Sáez-Valero, Javier Transmembrane Amyloid-Related Proteins in CSF as Potential Biomarkers for Alzheimer’s Disease |
title | Transmembrane Amyloid-Related Proteins in CSF as Potential Biomarkers for Alzheimer’s Disease |
title_full | Transmembrane Amyloid-Related Proteins in CSF as Potential Biomarkers for Alzheimer’s Disease |
title_fullStr | Transmembrane Amyloid-Related Proteins in CSF as Potential Biomarkers for Alzheimer’s Disease |
title_full_unstemmed | Transmembrane Amyloid-Related Proteins in CSF as Potential Biomarkers for Alzheimer’s Disease |
title_short | Transmembrane Amyloid-Related Proteins in CSF as Potential Biomarkers for Alzheimer’s Disease |
title_sort | transmembrane amyloid-related proteins in csf as potential biomarkers for alzheimer’s disease |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451586/ https://www.ncbi.nlm.nih.gov/pubmed/26082753 http://dx.doi.org/10.3389/fneur.2015.00125 |
work_keys_str_mv | AT lopezfontinmaculada transmembraneamyloidrelatedproteinsincsfaspotentialbiomarkersforalzheimersdisease AT cuchilloibanezinmaculada transmembraneamyloidrelatedproteinsincsfaspotentialbiomarkersforalzheimersdisease AT sogorbesteveaitana transmembraneamyloidrelatedproteinsincsfaspotentialbiomarkersforalzheimersdisease AT garciaayllonmariasalud transmembraneamyloidrelatedproteinsincsfaspotentialbiomarkersforalzheimersdisease AT saezvalerojavier transmembraneamyloidrelatedproteinsincsfaspotentialbiomarkersforalzheimersdisease |