Complement system and the brain: Selected pathologies and avenues toward engineering of neurological nanomedicines

Several nanoparticle systems and supramolecular assemblies are under investigation as potential therapeutic entities for Alzheimer's disease and other neurological disorders through both brain-specific targeting and peripheral effects. However, activation of the complement system, a complex innate immune network of over 30 circulating and membrane-bound proteins, remains a serious concern related to the use of these prospective neurological nanomedicines. The role of complement in processes of neurodegeneration in the injured or aged and diseased central nervous system is well known. Nanoparticle-mediated complement activation cannot only induce adverse cardiopulmonary distress in sensitive subjects, but may further aggravate the already-compromised condition of neurological disorders and diseases. This minireview briefly examines the role of complement in neurological diseases and outlines the current status of the development of key neurological nanomedicines with respect to complement activation. Understanding of these topics is crucial for rational design and development of safe neurological nanomedicines.