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Molecular Neurobiology

, Volume 52, Issue 3, pp 1391–1407 | Cite as

Aβ Influences Cytoskeletal Signaling Cascades with Consequences to Alzheimer’s Disease

  • Ana Gabriela Henriques
  • Joana Machado Oliveira
  • Liliana Patrícia Carvalho
  • Odete A. B. da Cruz e Silva
Article

Abstract

Abnormal signal transduction events can impact upon the cytoskeleton, affecting the actin and microtubule networks with direct relevance to Alzheimer’s disease (AD). Cytoskeletal anomalies, in turn, promote atypical neuronal responses, with consequences for cellular organization and function. Neuronal cytoskeletal modifications in AD include neurofibrillary tangles, which result from aggregates of hyperphosphorylated tau protein. The latter is a microtubule (MT)-binding protein, whose abnormal phosphorylation leads to MT instability and consequently provokes irregularities in the neuronal trafficking pathways. Early stages of AD are also characterized by synaptic dysfunction and loss of dendritic spines, which correlate with cognitive deficit and impaired brain function. Actin dynamics has a prominent role in maintaining spine plasticity and integrity, thus providing the basis for memory and learning processes. Hence, factors that disrupt both actin and MT network dynamics will compromise neuronal function and survival. The peptide Aβ is the major component of senile plaques and has been described as a pivotal mediator of neuronal dystrophy and synaptic loss in AD. Here, we review Aβ-mediated effects on both MT and actin networks and focus on the relevance of the elicited cytoskeletal signaling events targeted in AD pathology.

Keywords

Actin Tubulin Kinase Phosphatase Tau Cofilin 

Notes

Acknowledgments

This work was financed by the Fundação para a Ciência e Tecnologia of the Ministério da Educação e Ciência (JPND/0006/2011-BIOMARKAPD), the COMPETE program, QREN, and the European Union (Fundo Europeu de Desenvolvimento Regional) and also supported by PEst-OE/SAU/UI0482/2013.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Ana Gabriela Henriques
    • 1
  • Joana Machado Oliveira
    • 1
  • Liliana Patrícia Carvalho
    • 1
  • Odete A. B. da Cruz e Silva
    • 1
  1. 1.Laboratório de Neurociências e Sinalização, Centro de Biologia Celular, SACSUniversidade de AveiroAveiroPortugal

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