Intermediate Filaments as a Target of Signaling Mechanisms in Neurotoxicity

Abstract

In this chapter, we deal with the current knowledge and important results on the cytoskeletal proteins and their differential regulation by kinases/phosphatases and Ca 2+mediated mechanisms in developmental rat brain. We focus on the misregulation of the phosphorylating system associated with intermediate filament proteins of neural cells and its relevance to cell and tissue dysfunction. Taking into account our findings, we propose that intermediate-filament proteins are dynamic structures whose regulation is crucial for proper neural cell function. Given their relevance, they must be regulated in response to extracellular and intracellular signals. The complexity and connection between signaling pathways regulating intermediate-filament dynamics remain obscure. In this chapter, we get light into some kinase/phosphatase cascades downstream of membrane receptors disrupting the dynamics of intermediate filaments and its association with neural dysfunction. However, intermediate filaments do not act individually into the neural cells. Our results evidence the importance of misregulated cytoskeletal crosstalk in disrupting cytoskeletal dynamics and cell morphology underlying neural dysfunction in experimental conditions mimicking metabolic diseases and nongenomic actions of thyroid hormones and as an end point in the neurotoxicity of organic tellurium.

Astroglial Cells: Emerging Therapeutic Targets in the Management of Traumatic Brain Injury

“…At the site of insult, the amount of GFAP is related to the amount of reactive astroglial cells [179,180]. GFAP is an important intermediate filament that allows astrocytes to become hypertrophic through the synthesis of cytoskeletal structures and elongation of processes [181,182]. An increase in GFAP expression and hypertrophy is evident in the week following injury [183].…”