Title:Overall Role of Contactins Expression in Neurodevelopmental Events and
Contribution to Neurological Disorders
Volume: 22
Issue: 8
Author(s): Antonella Bizzoca, Emilio Jirillo, Paolo Flace and Gianfranco Gennarini*
Affiliation:
- Department of Basic Medical Sciences, Neurosciences, and Sensory Organs, Medical School, University of Bari,
Piazza Giulio Cesare, 11. Bari I-70124, Italy
Keywords:
Contactins, neural cell interactions, axonal growth control, neural development, neural morphogenesis, neural disorders, neural degeneration, friedreich ataxia.
Abstract:
Background: Neurodegenerative disorders may depend upon a misregulation of the pathways
which sustain neurodevelopmental control. In this context, this review article focuses on Friedreich
ataxia (FA), a neurodegenerative disorder resulting from mutations within the gene encoding the Frataxin
protein, which is involved in the control of mitochondrial function and oxidative metabolism.
Objective: The specific aim of the present study concerns the FA molecular and cellular substrates, for
which available transgenic mice models are proposed, including mutants undergoing misexpression of
adhesive/morphoregulatory proteins, in particular belonging to the Contactin subset of the immunoglobulin
supergene family.
Methods: In both mutant and control mice, neurogenesis was explored by morphological/morphometric
analysis through the expression of cell type-specific markers, including b-tubulin, the Contactin-1 axonal
adhesive glycoprotein, as well as the Glial Fibrillary Acidic Protein (GFAP).
Results: Specific consequences were found to arise from the chosen misexpression approach, consisting
of a neuronal developmental delay associated with glial upregulation. Protective effects against the
arising phenotype resulted from antioxidants (essentially epigallocatechin gallate (EGCG)) administration,
which was demonstrated through the profiles of neuronal (b-tubulin and Contactin 1) as well as
glial (GFAP) markers, in turn indicating the concomitant activation of neurodegeneration and neuro
repair processes. The latter also implied activation of the Notch-1 signaling.
Conclusion: Overall, this study supports the significance of changes in morphoregulatory proteins expression
in the FA pathogenesis and of antioxidant administration in counteracting it, which, in turn,
allows to devise potential therapeutic approaches.
