Complexing A[beta] Prevents the Cellular Anomalies Induced by the Peptide Alone

Retention of intracellular secreted APP (isAPP) can be provoked by the neurotoxic peptide A[beta]. The latter decreases in the cerebrospinal fluid of Alzheimer's disease (AD) patients, as a consequence of its cerebral accumulation and deposition into senile plaques. Of similar relevance, secret...

Full description

Saved in:
Bibliographic Details
Published in:Journal of molecular neuroscience 2014-08, Vol.53 (4), p.661
Main Authors: Henriques, A G, Oliveira, J M, Gomes, B, Ruivo, R, Da Cruz E Silva, E F, Da Cruz E Silva, O A, B
Format: Article
Language:English
Subjects:
Alzheimer's disease
Antibodies
Cerebrospinal fluid
Metabolism
Neurotoxicity
Peptides
Physiology
Polymerization
Proteins
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Retention of intracellular secreted APP (isAPP) can be provoked by the neurotoxic peptide A[beta]. The latter decreases in the cerebrospinal fluid of Alzheimer's disease (AD) patients, as a consequence of its cerebral accumulation and deposition into senile plaques. Of similar relevance, secreted APP (sAPP) levels can be associated with AD. The studies here presented, reinforce the link between sAPP and A[beta] and address putative therapeutic strategies. Laminin and gelsolin are potential candidates; both prevent A[beta] fibril formation by complexing with A[beta], thus attenuating its neurotoxicity. We show that preincubation of A[beta] with laminin and gelsolin has the effect of rendering it less potent to isAPP accumulation in cortical neurons. This appears to be related to a decrease in F-actin polymerization, whereas A[beta] alone induces the polymerization. Further, A[beta] decreases gelsolin levels, and the latter is involved in A[beta] removal. Our data indicates that A[beta]-laminin and A[beta]-gelsolin complexes are less neurotoxic and also less potent than fibrillar A[beta] at inducing isAPP retention. These results validate the potential of these proteins as therapeutic strategies that prevent the A[beta]-induced effects. In hence, given that A[beta] decreases the levels of proteins involved in its own clearance, this may contribute to the mechanisms underlying AD pathology.[PUBLICATION ABSTRACT]
ISSN:0895-8696
1559-1166
DOI:10.1007/s12031-014-0233-7