Scope of Lipid Nanoparticles in Neuroscience: Impact on the Treatment of Neurodegenerative Diseases.

BACKGROUND: Lipid nanoparticles have been studied mainly as a means of transporting and releasing drugs. A special emphasis has been placed on designing nanoparticles that improve the delivery of drugs with targets in the central nervous system. METHODS: The biomedical literature was searched for basic and clinical studies. The recent applications are described and related with their bioactivities. RESULTS: The current review compiles data on the components and features of lipid nanoparticle systems as well as the necessary conditions for their selective action. As an example of their application, we present data from preclinical and clinical studies on lipid nanoparticles used as potent and efficient agents in the diagnosis and treatment of some neurodegenerative maladies, including Parkinson's disease. CONCLUSION: Current evidence supports the application of lipid nanoparticles for designing drugs carriers for neurodegenerative diseases. Also, we have gathered data that suggests a role of drug-free lipid nanoparticles as neuroprotective or preventive agents during neurodegenerative processes.

Insights into the structural biology of G-protein coupled receptors impacts drug design for central nervous system neurodegenerative processes.

In the last few years, there have been important new insights into the structural biology of G-protein coupled receptors. It is now known that allosteric binding sites are involved in the affinity and selectivity of ligands for G-protein coupled receptors, and that signaling by these receptors involves both G-protein dependent and independent pathways. The present review outlines the physiological and pharmacological implications of this perspective for the design of new drugs to treat disorders of the central nervous system. Specifically, new possibilities are explored in relation to allosteric and orthosteric binding sites on dopamine receptors for the treatment of Parkinson's disease, and on muscarinic receptors for Alzheimer's disease. Future research can seek to identify ligands that can bind to more than one site on the same receptor, or simultaneously bind to two receptors and form a dimer. For example, the design of bivalent drugs that can reach homo/hetero-dimers of D2 dopamine receptor holds promise as a relevant therapeutic strategy for Parkinson's disease. Regarding the treatment of Alzheimer's disease, the design of dualsteric ligands for mono-oligomeric rinic receptors could increase therapeutic effectiveness by generating potent compounds that could activate more than one signaling pathway.