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Actin, cytoplasmic 1 (Beta-actin) and Actin, cytoplasmic 2 (Gamma-actin) are essential components of the eukaryotic cytoskeleton, existing in a dynamic equilibrium between monomeric G-actin and filamentous F-actin. In the nervous system, these isoforms are critical for neurogenesis, axon guidance, and the structural plasticity of dendritic spines, which underlies learning and memory (UniProt P60709, P63261). Mutations in ACTB and ACTG1 are associated with Baraitser-Winter cerebrofrontofacial syndrome, characterized by neuronal migration defects and intellectual disability (PubMed: 22366783). Furthermore, the formation of cofilin-actin rods and the loss of synaptic F-actin are implicated in the early stages of Alzheimer's disease and other neurodegenerative conditions (PubMed: 20404107). While small molecules like cytochalasins and latrunculins are widely used in research to inhibit actin polymerization, their clinical utility is limited by the ubiquitous nature of actin and the resulting systemic toxicity (DrugBank DB06754). Therapeutic strategies currently focus on targeting actin-regulatory proteins or developing isoform-specific modulators to restore synaptic function in neurological disorders.
Modulation of actin polymerization dynamics by either stabilizing filamentous actin (F-actin) or sequestering globular actin (G-actin) monomers to prevent assembly.
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