Role of Hemichannels in CNS Inflammation and the Inflammasome Pathway

Publication date: Available online 31 December 2015 Source:Advances in Protein Chemistry and Structural Biology Author(s): Yuri Kim, Joanne O. Davidson, Katherine C. Gunn, Anthony R. Phillips, Colin R. Green, Alistair J. Gunn Neurodegenerative, cardiovascular, and metabolic disorders, once triggered, share a number of common features, including sustained inflammatory cell activation and vascular disruption. These shared pathways are induced independently of any genetic predisposition to the disease or the precise external stimulus. Glial cells respond to injury with an innate immune response that includes release of proinflammatory cytokines and chemokines. Vascular endothelial cells may also be affected, leading to opening of the blood–brain barrier that facilitates invasion by circulating inflammatory cells. Inflammation can trigger acute neural injury followed by chronic inflammation that plays a key role in neurodegenerative conditions. Gap junction channels normally allow direct cell-to-cell communication. They are formed by the docking of two hemichannels, one contributed by each of the neighboring cells. While the opening probability of these channels is tightly controlled under resting conditions, hemichannels can open in response to injury or inflammatory factors, forming a large, relatively nonselective membrane pore. In this review, we consider the CNS immune system from the perspective that modulating connexin hemichannel opening can prevent tiss...
Source: Advances in Protein Chemistry and Structural Biology - Category: Biochemistry Source Type: research