Biomedical subjects

Christian Gonzalez-Billault

Publications and source records attributed to Christian Gonzalez-Billault.

4 recordsLinked to original sources

PubMed2007

Abeta1-42 stimulates actin polymerization in hippocampal neurons through Rac1 and Cdc42 Rho GTPases.

A number of psychiatric and neurodegenerative disorders, such as Alzheimer's disease, are characterized by abnormalities in the neuronal cytoskeleton. Here, we find that the enhancement in actin polymerization induced by fibrillar amyloid-beta peptide (Abeta) is associated with increased activity of Rac1/Cdc42 Rho GTPases. Rac1 upregulation involves the participation of Tiam1, a Rac guanine-nucleotide exchange factor, where Abeta exposure leads to Tiam1 activation by a Ca(2+)-dependent mechanism. These results point to Rho GTPases as one of the targets in Abeta-induced neurodegeneration in Alzheimer's disease pathology, with a role in mediating changes in the actin cytoskeletal dynamics.

Actins↗

PubMed2004

Microtubule-associated protein 1B function during normal development, regeneration, and pathological conditions in the nervous system.

Microtubule-associated protein 1B is the first MAP to be expressed during the development of the nervous system. Several different approaches have revealed that MAP1B function is associated with microtubule and actin microfilament polymerization and dynamics. In recent years, the generation of molecular models to inactivate MAP1B function in invertebrates and mammals has sparked some controversy about the real role of MAP1B. Despite discrepancies between some studies, it is clear that MAP1B plays a principal role in the development of the nervous system. In this article, we summarize the evidence for MAP1B function in a wide variety of cellular processes implicated in the proper construction of the nervous system. We also discuss the role of MAP1B in pathological processes.

Animals↗

PubMed2003

Iron-induced oxidative stress modify tau phosphorylation patterns in hippocampal cell cultures.

Oxidative stress phenomena have been related with the onset of neurodegenerative diseases. Particularly in Alzheimer Disease (AD), oxygen reactive species (ROS) and its derivatives can be found in brain samples of postmortem AD patients. However, the mechanisms by which oxygen reactive species can alter neuronal function are still not elucidated. There is a growing amount of evidence pointing to a role for mitochondrial damage as the source of free radicals involved in oxidative stress. Among the species that participate in the production of oxygen reactive radicals, transition metals are one of the most important. Several reports have implicated the involvement of redox-active metals with the onset of different neurodegenerative diseases such as Alzheimer's Disease (AD), Progressive Supranuclear Palsy (PSP), Amyotrophic Lateral Sclerosis (ALS) and Parkinson's Disease (PD). On the other hand, our previous studies have indicated that A beta-induced deregulation of the protein kinase Cdk5 associated with tau protein hyperphosphorylation constitute a critical pathway toward neurodegeneration. In the current paper we have shown that iron induces an imbalance in the function of Cdk5/p25 system of hippocampal neurons, resulting in a marked decrease in tau phosphorylation at the typical Alzheimer's epitopes. The loss of phosphorylated tau epitopes correlated with an increase in 4-hydroxy-nonenal (HNE) adducts revealing damage by oxidative stress. This effects on tau phosphorylation patterns seems to be a consequence of a decrease in the Cdk5/p25 complex activity that appears to result from a depletion of the activator p25, a mechanism in which calcium transients could be implicated.

Animals↗

PubMed2002

Microtubule-associated protein 1B is involved in the initial stages of axonogenesis in peripheral nervous system cultured neurons.

Neuronal process extension is dependent on the reorganisation of the cytoskeleton, in particular microtubules and microfilaments, and one of the ways in which microtubules are regulated is by a group of microtubule-associated proteins called MAPs. MAP1B, the first MAP to be expressed in developing neurons, has been shown to play an important role during axonogenesis. Previously, we have shown that a phosphorylated isoform of MAP1B is involved in maintaining growth cone microtubules in a dynamically unstable state. In order to further investigate the role of MAP1B during axonogenesis we have cultured dorsal root ganglion (DRG) neurons from a MAP1B deficient mutant mouse. These mice express only trace amounts of MAP1B, have defects in the development of their nervous system and die perinatally. Cultured DRG neurons from MAP1B deficient mice show a reduction in axon elongation and an increase in growth cone area. The reduction in axon elongation is most likely to occur due to an inhibition in the early stages of axonogenesis. Using time-lapse video we have verified that during the first 2 h after plating, MAP1B deficient neurones extend their axons with an average speed that is half the speed of control neurones. These results support the participation of MAP1B during the initial stages of axonogenesis.

Animals↗