The Role of Atypical Chemokine Receptors in Neuroinflammation and Neurodegenerative Disorders

Neuroinflammation is associated with several neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). Neuroinflammation provides protection in acute situations but results in significant damage to the nervous system if chronic. Overexpression of chemokines within the brain results in the recruitment and activation of glial and peripheral immune cells which can propagate a cascading inflammatory response, resulting in neurodegeneration and the onset of neurodegenerative disorders. Recent work has identified the role of atypical chemokine receptors (ACKRs) in neurodegenerative conditions. ACKRs are seven-transmembrane domain receptors that do not follow canonical G protein signaling, but regulate inflammatory responses by modulating chemokine abundance, location, and availability. This review summarizes what is known about the four ACKRs and three putative ACKRs within the brain, highlighting their known expression and discussing the current understanding of each ACKR in the context of neurodegeneration. The ability of ACKRs to alter levels of chemokines makes them an appealing therapeutic target for neurodegenerative conditions. However, further work is necessary to understand the expression of several ACKRs within the neuroimmune system and the effectiveness of targeted drug therapies in the prevention and treatment of neurodegenerative conditions.