NANOPARTICLE-BASED MODULATION OF NEURONAL ACTIVITY AND NEUROPROTECTION IN PARKINSON’S AND ALZHEIMER’S DISEASE

Abstract

Parkinson's disease (PD) and Alzheimer's disease (AD) are diseases which affect more than 50 million people worldwide but there are no known disease modifying therapies. Small molecule drugs and virtually no biologics are able to cross the blood-brain barrier (BBB). The introduction of a platform technology that would cross the BBB and deliver neuroprotective agents in a controlled manner, along with modulation of neuronal activity through external physical stimuli like light or magnetic fields, has made nanoparticles a transformative solution. The current critical review deals with the use of nanoparticles in the context of neuroprotection and direct neuromodulation in PD and AD. The platforms that are neuroprotective are: antioxidant (cerium oxide); anti-aggregation (curcumin-PLGA, gold nanoparticles); anti-inflammatory (minocycline lipid nanoparticles); neurotrophic factor carrier (GDNF-PLGA, BDNF-chitosan); and gene therapy vectors (CRISPR-Cas9 lipid nanoparticles, siRNA-loaded exosomes). The different strategies of neuromodulation include photothermal (use of gold nanoparticles and near-infrared light), magnetothermal (use of iron oxide nanoparticles and alternating magnetic fields), ultrasound-sensitive nanodroplets, and nanoparticle-enhanced optogenetics. There is also a review of theranostic nanoparticles that combine MRI, fluorescence or PET with therapy. Preliminary findings in rodent models show a decrease in protein aggregation, oxidative stress, and neuroinflammation, as well as increased dopamine levels and enhanced motor and cognitive function. Subchronic study shows that biodegradable formulations are safe. The clinical translation is also in its early stages and includes ferumoxytol (MRI) and nanoliposomal curcumin (Phase I). This is set to evolve into customised targeting, closed-loop release and machine learning-based design in the future