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

Autor: Robinson AP; Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Zhang JZ; Clene Nanomedicine, Inc., Salt Lake City, UT, USA., Titus HE; Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Karl M; George Washington University, Washington, DC, USA., Merzliakov M; Clene Nanomedicine, Inc., Salt Lake City, UT, USA., Dorfman AR; Clene Nanomedicine, Inc., Salt Lake City, UT, USA., Karlik S; Lawson Health Research Institute, London Health Sciences Center, Ontario, Canada., Stewart MG; Brigham Young University, Provo, UT, USA., Watt RK; Brigham Young University, Provo, UT, USA., Facer BD; Vanderbilt University School of Medicine, Nashville, TN, USA., Facer JD; Brigham Young University, Provo, UT, USA., Christian ND; Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA., Ho KS; Clene Nanomedicine, Inc., Salt Lake City, UT, USA. karen@clene.com.; University of Utah School of Medicine, Salt Lake City, UT, USA. karen@clene.com., Hotchkin MT; Clene Nanomedicine, Inc., Salt Lake City, UT, USA., Mortenson MG; Clene Nanomedicine, Inc., Salt Lake City, UT, USA., Miller RH; George Washington University, Washington, DC, USA., Miller SD; Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Feb 11; Vol. 10 (1), pp. 1936. Date of Electronic Publication: 2020 Feb 11.
DOI: 10.1038/s41598-020-58709-w
Abstrakt: 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.
Databáze: MEDLINE
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