@article{97ed82fd414847bba63193226f3b9bce,
title = "Nanocatalytic activity of clean-surfaced, faceted nanocrystalline gold enhances remyelination in animal models of multiple sclerosis",
abstract = "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.",
author = "Robinson, {Andrew P.} and Zhang, {Joanne Zhongyan} and Titus, {Haley E.} and Molly Karl and Mikhail Merzliakov and Dorfman, {Adam R.} and Stephen Karlik and Stewart, {Michael G.} and Watt, {Richard K.} and Facer, {Benjin D.} and Facer, {Jon D.} and Christian, {Noah D.} and Ho, {Karen S.} and Hotchkin, {Michael T.} and Mortenson, {Mark G.} and Miller, {Robert H.} and Miller, {Stephen D.}",
note = "Funding Information: We thank Drs. Robert Glanzman and Glen Frick for critical reading of the manuscript, and gratefully acknowledge the technical and intellectual support of all our fellow colleagues at Clene Nanomedicine, Inc. The guidance and expert leadership CEO Rob Etherington is greatly valued and appreciated. We thank Pieter D{\textquoteright}Arnaud of Instat, Inc. for help with statistical analyses of the cuprizone remyelination and fine motor kinetic data. We thank Dr. Damiano Fantini, Matthew J. Schipma and the staff at the NuSeq core (Northwestern University) for sequencing the RNAseq libraries and preliminary statistical analysis of sequence data (test statistic, p-value, false discovery rate), and especially Dr. Fantini for preliminary bioinformatics analyses. We also thank Carol Cooke of the Electron Microscopy Lab in the Neurology Department of Johns Hopkins University for technical TEM help. Cellomet, Neuro/sys, and Charles River Labs performed contracted research for us. This study was funded by Clene Nanomedicine, Inc. Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41598-020-58709-w",
language = "English (US)",
volume = "10",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}