Tau Targeting Therapies Study

Background of Tau Targeting Therapies Study

The microtubule-associated protein tau is involved in multiple biological activities, such as microtubule stabilization and assembly, maintaining neuronal cytoskeleton, and axonal transportation. The onset of clinical symptoms of Alzheimer's disease (AD) is a chronic process. Tau pathology in neurodegenerative AD usually initiates from the accumulation of neurofibrillary tau tangles. Current clinical trials and drugs targeting tau kinase inhibitors have shown only a little efficacy. Monoclonal antibody therapies targeting tau may be the future of drug development. Understanding the mechanisms of tau action in AD assists researchers in better comprehending AD pathogenesis. Here, Creative Biolabs is committed to providing a wide range of in vivo, in vitro, and ex vivo assays in the field of neuroscience translational studies, which enable researchers to investigate the mystery of tau mechanism of action (MoA) in AD and hence develop drugs targeting neurotoxic tau aggregates in the early stage.

Tau MoA in AD

Tau can be subjected to several post-translational modifications such as phosphorylation and truncation. However, the aberrant post-translational modifications under pathogenic conditions lead to tau fragmentation from microtubules to form pathologic hyperphosphorylated and truncated tau species. Then the formation and accumulation of tau aggregates and tau oligomers will exacerbate the pathologic process of AD. Tau oligomers can lead to subsequent intracellular aggregation of paired helical tau filaments and neurofibrillary tau tangles in neurons. Those pathologic tau species then enter post-synapses impairing long-term potentiation through modulating Fyn/NMDAR complexes. Additionally, tau aggregates also damage the normal function of synapses through the impairments of mitochondria, synaptic vesicle mobility, and neurotransmitter release. Extracellular pathogenic tau proteins are absorbed in neurons via a heparan sulfate proteoglycans (HSPGs)-mediated pathway, causing intracellular tau accumulation. Moreover, extracellular pathogenic tau species induce neuroinflammation by activating microglia via nuclear factor kappa-B and NLRP3 pathways releasing pro-inflammatory cytokines, which also enhance the activity of tau kinases and aggravate tau hyperphosphorylation.

Fig.1 A model for tau pathogenesis in AD. (Guo, 2020)

Related Services at Creative Biolabs

A variety of tau targeting therapies study services are available in Creative Biolabs to meet your research and preclinical drug development requirements. We offer a full range of tau-related assays, including tau phosphorylation assay, tau hyperphosphorylation assay, tau aggregation assay, tau uptake and seeding assay, tau clearance assay, etc. Our advanced high-throughput imaging techniques, electrophysiology tools, and behavioral testing platforms enable researchers to study tau protein in AD pathogenesis, hence developing tau targeting therapies for AD. If you have the intention to study tau in AD, please don't hesitate to contact us. Our professional team will help you to design the optimal solution.

Reference

1. Guo, T.; et al. Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer's disease. Molecular neurodegeneration. 2020, 15(1): 1-37.