P2x7 receptor is a new terapeutic target to treat tauopathies

Resumo

Tau is a highly soluble microtubule-associated protein (MAP) that in brain is mainly expressed in neurons. Its major role in neurons, especially in axons, is to stabilize the microtubules, regulating their assembly, growing, and shortening in a phosphorylation-dependent way (Buée et al., 2000). The accumulation of hyperphosphorylated tau, with the consequent aggregation into paired helical filaments (PHFs) and formation of neurofibrillary tangles (NFTs), has been described as characteristic feature of a family of neurodegenerative disease collectively known as Tauopathies. This disease family comprises several pathological conditions, including Alzheimer’s Disease (AD), the most common tauopathy, Pick’s disease (PiD), corticobasal degeneration and post-encephalic parkinsonism (Williams, 2006). Tauopathies can show different clinical phenotypes ranging from neuronal loss and reduced synaptic density, with consequent dementia, to behavioural and movement disorders (Lee et al., 2001; Williams, 2006). Although neither the exact causing factors of NFTs aggregation nor the mechanism leading to neuronal and synaptic loss has been elucidated, it has been demonstrated that neuroinflammation is linked to early progression of tauopathies (Metcalfe et al., 2010). Neuroinflammation is an active inflammatory response within the brain characterized by the production of inflammatory mediators and mainly mediated by microglia cells, the innate immune cells of the central nervous system (DiSabato et al., 2016). In addition to inflammatory mediators, other endogenous molecules, known as damage-associated molecular patterns (DAMPs), are secreted from injured cells. These molecules include adenosine triphosphate (ATP), which is released in large amount into the extracellular space during neuroinflammation (Newton and Dixit, 2012)...