![platinum intools platinum intools](https://i1.rgstatic.net/publication/349991333_The_Cellular_Senescence_Stress_Response_in_Post-Mitotic_Brain_Cells_Cell_Survival_at_the_Expense_of_Tissue_Degeneration/links/604a4eba92851c1bd4dfb0b9/largepreview.png)
Unlike bulk gold, which does not corrode and is generally recognized as chemically inert, gold at the nanoscale can be highly catalytic. Here we describe a new nanocatalytic therapeutic candidate for remyelination consisting of a suspension of clean-surfaced, faceted nanocrystals of gold. The enhancement of the glycolytic pathway has been proposed as a potential therapeutic target for remyelination in MS 7. Aerobic glycolysis results in production of pyruvate, acetyl coenzyme A, and NADPH, the requisite precursors of myelin proteins and lipids. Under favourable growth conditions, human OPCs and OLs preferentially utilize aerobic glycolysis over oxidative phosphorylation for energy generation, resulting in an enhanced capacity to differentiate and myelinate axons 7. Similarly, cultured human OLs, placed under metabolic stress using low glucose media, retract their cellular processes and exhibit significantly reduced glycolytic activity, favouring cell survival at the expense of myelin stability 7, 8. These OPCs fail to remyelinate and exhibit markers of metabolic stress 6. Limited remyelination occurs in multiple sclerosis (MS) lesions despite the presence of OPCs in or around lesion sites. During active myelination, OLs synthesize on the order of 100,000 proteins per minute 2 and several thousand new lipid molecules per second 3, reflecting the significant energetic investment needed for biomass generation, and making this cell type among the most energetically demanding of the body.ĭysregulated energy metabolism impacting OLs has been postulated to play a central role in MS disease progression 4, 5.
![platinum intools platinum intools](https://static.cdn.asset.aparat.com/avt/9319262-3076__1179.jpg)
Myelination is a complex process by which axons are wrapped with oligodendrocyte (OL) membranes containing specialized proteins and lipids, facilitating axonal electrical conduction and providing essential trophic support to neurons 1. Based on these preclinical studies, clean-surfaced, faceted gold nanocrystals represent a novel remyelinating therapeutic for multiple sclerosis.
![platinum intools platinum intools](https://i2.wp.com/paktechpoint.com/wp-content/uploads/2021/02/img_6018178b79ef5.png)
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. 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. Gold nanocrystal treatment of oligodendrocyte precursor cells in culture resulted in oligodendrocyte maturation and expression of myelin differentiation markers. Furthermore, oral delivery of gold nanocrystals improved motor functions of cuprizone-treated mice in both open field and kinematic gait studies. 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. 2016.v18.0.Win32.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.
#PLATINUM INTOOLS WINDOWS#
Landmark DSD Geoprobe 5000.8.3 5000.10 windows linux Paradigm epos geodepth gocad skua geolog sysdrill StratEarth 2015 Output guide STL : Three dimensional digital dental implant design system