Microtubule-associated protein tau oligomer (TauO) (TauO)

Microtubule-associated protein tau (MAPT) is a protein primarily located in neuronal axons, where it plays a vital role in stabilizing microtubules and supporting axonal transport [8, 24]. In neurodegenerative conditions known as tauopathies, tau becomes hyperphosphorylated and detaches from microtubules, subsequently aggregating into soluble tau oligomers [1, 18]. These oligomers are now considered the most neurotoxic species in diseases like Alzheimer's, as they disrupt synaptic plasticity, impair mitochondrial function, and inhibit fast axonal transport [5, 16, 21]. Unlike insoluble neurofibrillary tangles, tau oligomers are highly diffusible and can spread pathology between neurons in a prion-like manner [7, 17, 23]. Therapeutic approaches targeting these species include monoclonal antibodies (e.g., Gosuranemab, Semorinemab) that aim to clear extracellular tau and block its spread, as well as small molecule inhibitors (e.g., Hydromethylthionine mesylate) that prevent the initial stages of aggregation [9, 15]. Additionally, antisense oligonucleotides like BIIB080 are being investigated to reduce total tau levels, thereby decreasing the pool available for oligomer formation [13, 15]. Key challenges in drug development include achieving sufficient blood-brain barrier penetration and ensuring that the reduction of pathological tau does not interfere with its essential physiological functions [1, 13].

Other names

Tau aggregatesSoluble tau oligomersPre-fibrillar tauPathogenic tauTauOTauOs

Inhibition of tau aggregation, clearance of extracellular tau via passive immunotherapy, and reduction of tau protein synthesis using antisense oligonucleotides.