Mitochondrial dysregulation occurs early in ALS motor cortex with TDP-43 pathology and suggests maintaining NAD+ balance as a therapeutic strategy was written by Gautam, Mukesh;Gunay, Aksu;Chandel, Navdeep S.;Ozdinler, P. Hande. And the article was included in Scientific Reports in 2022.Electric Literature of C11H15N2O8P The following contents are mentioned in the article:
Mitochondrial defects result in dysregulation of metabolomics and energy homeostasis that are detected in upper motor neurons (UMNs) with TDP-43 pathol., a pathol. that is predominantly present in both familial and sporadic cases of amyotrophic lateral sclerosis (ALS). While same mitochondrial problems are present in the UMNs of ALS patients with TDP-43 pathol. and UMNs of TDP-43 mouse models, and since pathologies are shared at a cellular level, regardless of species, we first analyzed the metabolite profile of both healthy and diseased motor cortex to investigate whether metabolomic changes occur with respect to TDP-43 pathol. High-performance liquid chromatog., high-resolution mass spectrometry and tandem mass spectrometry (HPLC-MS/MS) for metabolite profiling began to suggest that reduced levels of NAD+ is one of the underlying causes of metabolomic problems. Since NMN (NMN) was reported to restore NAD+ levels, we next investigated whether NMN treatment would improve the health of diseased corticospinal motor neurons (CSMN, a.k.a. UMN in mice). prpTDP-43A315T-UeGFP mice, the CSMN reporter line with TDP-43 pathol., allowed cell-type specific responses of CSMN to NMN treatment to be assessed in vitro. Our results show that metabolomic defects occur early in ALS motor cortex and establishing NAD+ balance could offer therapeutic benefit to UMNs with TDP-43 pathol. This study involved multiple reactions and reactants, such as ((2R,3S,4R,5R)-5-(3-Carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl hydrogen phosphate (cas: 1094-61-7Electric Literature of C11H15N2O8P).
((2R,3S,4R,5R)-5-(3-Carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl hydrogen phosphate (cas: 1094-61-7) belongs to amides. Compared to amines, amides are very weak bases and do not have clearly defined acid–base properties in water. On the other hand, amides are much stronger bases than esters, aldehydes, and ketones. Amides can be recrystallised from large quantities of water, ethanol, ethanol/ether, aqueous ethanol, chloroform/toluene, chloroform or acetic acid. The likely impurities are the parent acids or the alkyl esters from which they have been made. The former can be removed by thorough washing with aqueous ammonia followed by recrystallisation, whereas elimination of the latter is by trituration or recrystallisation from an organic solvent.Electric Literature of C11H15N2O8P
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics