Central nervous system agents in medicinal chemistry
In this review we describe effects and mechanism of action of α7 nAChR and RIC-3 in the immune cholinergic system. Elucidating these mechanisms and the regulation of α7 and RIC-3 in the immune cholinergic system can pave the way for novel immunomodulatory agents, or towards extending the application of cholinergic agents.
BackgroundThe nicotinic acetylcholine receptors form a large and diverse family of acetylcholine gated ion channels having diverse roles in the central nervous system. Maturation of nicotinic acetylcholine receptors is a complex and inefficient process requiring assistance from multiple cellular factors including RIC-3, a functionally conserved end...
BackgroundRecent work has shown that the chaperone resistant to inhibitors of acetylcholinesterase (RIC-3) is critical for the folding, maturation and functional expression of a variety of neuronal nicotinic acetylcholine receptors. α7 nicotinic receptors can only assemble and functionally express in select lines of cells, provided that RIC-3 is pr...
BBA - Biomembranes
Highlights► The α7 nicotinic acetylcholine receptor (AChR) is one of the most abundant AChR subtypes in the hippocampus. ► This receptor is a potential therapeutic target for important psychiatric diseases. ► RIC-3, a protein originally found in C. elegans, modulates the expression of α7 receptors. ► Modulation of receptor expression by RIC-3 is cr...
Journal of neurochemistry
Mechanisms that regulate early events in the biogenesis of the alpha7 nicotinic acetylcholine receptor (alpha7 AChR) are not well understood. Data presented here show that single amino acid mutations in the cytoplasmic loop of the alpha7 AChR, between position 335 and 343, abolish or attenuate expression of mature pentameric alpha7 AChRs in both hu...
British journal of pharmacology
RIC-3 is a transmembrane protein which acts as a molecular chaperone of nicotinic acetylcholine receptors (nAChRs). For some nAChR subtypes (such as homomeric alpha7 neuronal nAChRs), RIC-3 is required for efficient receptor folding, assembly and functional expression. In contrast, for other nAChR subtypes (such as heteromeric alpha4beta2 neuronal ...