GliaNFish · Glial-neuron crosstalk in the regulation of neurofilament dynamics

Glial-neuron crosstalk in the regulation of neurofilament dynamics

Every cell in the human body contains an internal scaffold known as the cytoskeleton, which plays a vital role in maintaining cellular structure, stability, and function. The cytoskeleton consists of three major components: actin filaments, microtubules, and intermediate filaments. In neurons, the intermediate filament network is mainly composed out of neurofilaments, which ensures the integrity and organisation of the neuronal cytoskeleton. Increasing evidence suggests that neurodegenerative diseases are not only associated with abnormalities in the cytoskeletal network, but are also driven by them. Disorganisation and dysregulation of neurofilaments are common pathological features in a wide range of neurodegenerative conditions, even in cases where there are no mutations in the gene encoding neurofilaments itself. Furthermore, experimental studies have shown that targeted manipulation of neurofilaments can improve disease outcomes, highlighting it as a promising and underexplored therapeutic target. Despite this, the precise role of neurofilaments in healthy neuronal physiology and neurological disease remains poorly understood. The goal of the GliaNFish project was to investigate the dynamics and organisation of neurofilaments in vivo, both during normal neuronal development and under pathological conditions. Using zebrafish as a model organism, the project aimed to visualise and characterise neurofilament transport and organization in real time, allowing to study its function in the context of a living, developing nervous system. To study the impact of disease, the project focussed on two disease-related genetic alterations: 1) mutations in frataxin, known to cause the autosomal recessive ataxia Friedreich’s ataxia and 2) a recently discovered gene duplication in a gene previously associated with inherited neuropathies. By creating and characterising zebrafish models that replicate these human disease mutations, the project aims to gain a better understanding of the disease pathology and explore how genetic disruptions influence neurofilament organization.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз