Nanocatalytic activity of clean-surfaced, faceted nanocrystalline gold enhances remyelination in animal models of multiple sclerosis

• Published in: Scientific reports Vol. 10; no. 1; p. 1936
• Main Authors: Robinson, Andrew P., Zhang, Joanne Zhongyan, Titus, Haley E., Karl, Molly, Merzliakov, Mikhail, Dorfman, Adam R., Karlik, Stephen, Stewart, Michael G., Watt, Richard K., Facer, Benjin D., Facer, Jon D., Christian, Noah D., Ho, Karen S., Hotchkin, Michael T., Mortenson, Mark G., Miller, Robert H., Miller, Stephen D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.02.2020; Nature Publishing Group
• Subjects: 631/154/433; 692/617/375; Adenine; Animal models; Animals; Apoptosis - drug effects; Biomechanical Phenomena - drug effects; Cell culture; Cell Movement - drug effects; Central nervous system; Crystals; Cuprizone; Demyelination; Disease Models, Animal; Drug therapy; Energy metabolism; Gait; Gene Expression Profiling; Glial stem cells; Glycolysis; Gold; Humanities and Social Sciences; Lactic acid; Metal Nanoparticles - administration & dosage; Metal Nanoparticles - therapeutic use; Mice; Movement - drug effects; multidisciplinary; Multiple sclerosis; Multiple Sclerosis - chemically induced; Multiple Sclerosis - drug therapy; Multiple Sclerosis - pathology; Myelin; Myelination; NAD; Nanocrystals; Neuroprotection; Nicotine; Oligodendrocyte Precursor Cells - drug effects; Oligodendrocyte Precursor Cells - pathology; Remyelination - drug effects; Science; Science (multidisciplinary); Signal Transduction - drug effects; Signal Transduction - genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-58709-w

Development of pharmacotherapies that promote remyelination is a high priority for multiple sclerosis (MS), due to their potential for neuroprotection and restoration of function through repair of demyelinated lesions. A novel preparation of clean-surfaced, faceted gold nanocrystals demonstrated robust remyelinating activity in response to demyelinating agents in both chronic cuprizone and acute lysolecithin rodent animal models. Furthermore, oral delivery of gold nanocrystals improved motor functions of cuprizone-treated mice in both open field and kinematic gait studies. Gold nanocrystal treatment of oligodendrocyte precursor cells in culture resulted in oligodendrocyte maturation and expression of myelin differentiation markers. Additional in vitro data demonstrated that these gold nanocrystals act via a novel energy metabolism pathway involving the enhancement of key indicators of aerobic glycolysis. In response to gold nanocrystals, co-cultured central nervous system cells exhibited elevated levels of the redox coenzyme nicotine adenine dinucleotide (NAD+), elevated total intracellular ATP levels, and elevated extracellular lactate levels, along with upregulation of myelin-synthesis related genes, collectively resulting in functional myelin generation. Based on these preclinical studies, clean-surfaced, faceted gold nanocrystals represent a novel remyelinating therapeutic for multiple sclerosis.