Human actinopathies are a group of rare autosomal dominant disorders caused by heterozygous missense mutations in genes encoding actin. In particular, mutations in the ACTG1 gene, encoding the γ-cytoskeletal actin, a major isoform in neuronal cells, lead to diseases known as Non-Muscle Actinopathies (NMAs), which may result in severe neurological symptoms.

In developing neurons, the actin cytoskeleton has a crucial involvement in neurite formation, elongation, branching, signal transduction, formation of synaptic structures and in neuronal migration process. In mature neurons, actin is the predominant cytoskeletal component of synapses, both at the pre- and postsynaptic levels. Mutations in actin genes can alter the stability or polymerization of actin filaments, impairing the protein's functionality and causing significant morphological and functional changes in neuronal cells.

In this study, patient-derived induced Pluripotent Stem Cells (iPSCs), wild-type or harboring mutations in the ACTG1 gene, are differentiated in neuronal cells. Our team utilizes electrophysiology and immunofluorescent microscopy to analyze the relationship between actin mutation and cellular functionality and morphology.

This research is part of the ‘MAS-NeurActin’  project, in collaboration with the University of Florence and CNR of Florence, funded by the Ministry of Education, Universities and Research (MUR) as part of the ‘PRIN: Projects of National Interest’ initiative.