Author response: A chemical proteomic atlas of brain serine hydrolases identifies cell type-specific pathways regulating neuroinflammation
Year: 2015
Type: peer-review
Abstract: The brain is made up of many types of cells. These include the neurons that transmit messages throughout the nervous system, and microglia, which act as the first line of the brain’s immune defense. The activity of both neurons and microglia can be influenced by molecules called endocannabinoids that bind to proteins on the cells’ surface. For example, endocannabinoids affect how a neuron responds to messages sent to it from a neighbouring neuron, and help microglia to regulate the inflammation of brain tissue. Enzymes called serine hydrolases play important roles in several different signaling processes in the brain, including those involving endocannabinoids. Viader et al. have now studied the activities of these enzymes – including two called DAGLα and DAGLβ – in the mouse brain using a technique called activity-based protein profiling. This revealed that DAGLα plays an important role in controlling how neurons respond to endocannabinoids, while DAGLβ performs the equivalent role in microglia. When Viader et al. shut down DAGLβ activity, this only affected endocannabinoid signaling in microglia. This also had the effect of reducing inflammation in the brain, without affecting how endocannabinoids signal in neurons. These results suggest that inhibitors of DAGLβ could offer a way to suppress inflammation in the brain, which may contribute to neuropsychiatric and neurodegenerative diseases, while preserving the normal pathways that neurons use to communicate with one another.
Institution: Scripps Research Institute
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W2987151015