Regulator of the F-actin-based cytoskeleton

The Regulator of the F-actin-based cytoskeleton is a novel therapeutic target involved in the modulation of actin dynamics within neuronal synapses. It is specifically targeted by the clinical-stage small molecule SPG302 (tazbentetol), which is designed to restore synaptic density and function in neurodegenerative and neuropsychiatric disorders [1, 2]. This target plays a critical role in the formation and stabilization of branched F-actin assemblies, which are essential for the structural integrity of dendritic spines and the maintenance of glutamatergic synapses [1, 6]. In diseases like Alzheimer's and ALS, synaptic loss is a primary driver of cognitive and motor decline; by activating this regulator, SPG302 promotes the regeneration of lost synapses and improves neuronal communication [5, 12]. Preclinical studies have shown that targeting this molecule can reverse cognitive deficits and increase the expression of key synaptic proteins like PSD-95 and drebrin without affecting amyloid or tau pathology [1, 13]. SPG302 is a third-generation pegylated benzothiazole derivative that exhibits high selectivity for this regulator, and early clinical trials have demonstrated that modulating this target is well-tolerated with potential for significant functional improvements [7, 16].

Other names

Synaptic F-actin regulatorRegulator of F-actin dynamicsSPG302 targetRegulator of F-actin dynamics protein 1

Promotion of branched F-actin assembly and restoration of dendritic spine density