title: Aβ Influences Cytoskeletal Signaling Cascades with Consequences to Alzheimer's Disease.
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.
authors.affiliation: Laboratório de Neurociências e Sinalização, Centro de Biologia Celular, SACS, Universidade de Aveiro, 3810-193, Aveiro, Portugal.
authors.forename: Ana Gabriela
authors.initials: AG
authors.lastname: Henriques
authors.affiliation: Laboratório de Neurociências e Sinalização, Centro de Biologia Celular, SACS, Universidade de Aveiro, 3810-193, Aveiro, Portugal.
authors.forename: Joana Machado
authors.initials: JM
authors.lastname: Oliveira
authors.affiliation: Laboratório de Neurociências e Sinalização, Centro de Biologia Celular, SACS, Universidade de Aveiro, 3810-193, Aveiro, Portugal.
authors.forename: Liliana Patrícia
authors.initials: LP
authors.lastname: Carvalho
authors.affiliation: Laboratório de Neurociências e Sinalização, Centro de Biologia Celular, SACS, Universidade de Aveiro, 3810-193, Aveiro, Portugal. odetecs@ua.pt.
authors.forename: Odete A B
authors.initials: OAB
authors.lastname: da Cruz E Silva
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology / Q000648:ultrastructure; D000199:Actins / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000502:physiology*; D051338:Cofilin 1 / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D049229:Dendritic Spines / Q000648:ultrastructure; D006801:Humans; D007858:Learning / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology; D008568:Memory / Q000502:physiology; D008870:Microtubules / Q000502:physiology / Q000648:ultrastructure; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000502:physiology*; D016874:Neurofibrillary Tangles; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010749:Phosphoprotein Phosphatases / Q000502:physiology; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000737:chemistry / Q000648:ultrastructure; D011494:Protein Kinases / Q000502:physiology; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D014404:Tubulin / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D000199:Actins; D016229:Amyloid beta-Peptides; D051338:Cofilin 1; C054369:MAPT protein, human; D009419:Nerve Tissue Proteins; D014404:Tubulin; D016875:tau Proteins; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases
keywords: Actin; Cofilin; Kinase; Phosphatase; Tau; Tubulin