About this Research Topic
Despite differences in disease etiology (e.g. β-amyloid, polyglutamine expansion or neurodevelopmental abnormalities), several brain diseases (e.g. Alzheimer's disease, epilepsy or schizophrenia) share common clinical symptoms with overlapping diagnoses including depression, psychotic episodes, cognitive deficits, anxiety and seizures. This implies shared pathological pathway activation among different brain diseases. An emerging concept is that increased hyperexcitability and network changes are universal patho-mechanisms in numerous brain diseases, caused and maintained by a sustained glial activation. As well as neurons, glial cells are involved in network hyperexcitability and the mediation of inflammatory processes by modulating the release of neurotransmitters and pro-inflammatory cytokines.
The cation-permeable ionotropic ATP-gated purinergic P2X7 receptor, activated in multiple diseases of the central nervous system (CNS), expressed throughout the brain and mainly activated under the pathological conditions of high ATP release represents a potential link between neuronal hyperexcitability and glia-driven pro-inflammatory signaling.
Studies attribute a wide array of pathological functions to P2X7 in the brain, most prominently the activation of pro-inflammatory processes and regulation of neurotransmitter release. P2X7 activation has also been linked to other damaging processes shared by the majority of brain diseases such as the promotion of cell death, hyperexcitability and opening of the blood brain barrier, potentially contributing to both primary disease pathology and associated co-morbidities. Critically, increasing data demonstrates beneficial effects of P2X7 antagonism on pathology in several brain diseases including neurodegenerative, psychiatric and neurological diseases.
The aim of this Research Topic is to provide an overview of the therapeutic potential of P2X7 antagonism covering a broad range of different brain diseases and highlight novel developments of pharmacological and genetic tools to study P2X7 signaling in vivo.
Keywords: Brain diseases, Shared pathology, ATP, P2X7 receptor
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