Explore chapters and articles related to this topic
Mitochondrial Dysfunction in Huntington Disease
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Md. Hafiz Uddin, Marufa Rumman, Tasnuva Sarowar
The experimental compound olesoxime, a mitochondria-targeting cholesterol derivative, has shown promise in preclinical models. Olesoxime interacts with the mitochondrial membrane (MMs) and stabilizes calcium signaling through the regulation of VDAC of the outer mitochondrial membrane (Eckmann et al. 2014). Minocycline, an anti-inflammatory drug, showed promising results through acting on antioxidants and other systems. It is a tetracycline derivative that particularly binds to MMs and modulates Ca2+ signaling via mPTP (Figure 9.2) (Antonenko et al. 2010; Kim and Suh 2009; Fernandez-Gomez et al. 2005). Sirtuins emerge as a novel target (Shih and Donmez 2013), and targeting mitochondrial SIRT3 by viniferin has already shown effectiveness in the preclinical STHdhQ111/Q111 mice model (Fu et al. 2012). Major preclinical and clinical studies with natural and synthetic compounds for the treatment or prevention of HD are summarized in Table 9.1.
Pharmacological Management of Amyotrophic Lateral Sclerosis
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Shalini Mani, Chahat Kubba, Tanya Sharma, Manisha Singh
Treatment of ALS using anti-excitotoxins is still in active research phase and has shown a promising clinical outcome (Venkova-Hristova et al., 2017). The benzothiazole compound R-pramipexole came into view as a drug from research on Parkinson’s disease that can save dopaminergic neurons from glutamate excitotoxicity. The neuroprotective effects observed to be triggered downstream from the glutamate-gated receptors and further intended to perform action in the mitochondria (Izumi et al., 2007). Thus, potential neuroprotective compounds are hypothesized to have a considerable clinical benefit in ALS patients. Unsurprisingly, therapeutic approach that belongs to this class has recruited numerous patients in their respective phase 3 trials. Clinical trials with TCH346 (Miller et al., 2007) and olesoxime (Lenglet et al., 2014) have recruited more than 500 patients each, with dexpramipexole (Cudkowicz et al., 2011) and xaliproden (Lacomblezetal, 2004) recruiting more than 1000 and 2000 patients, respectively. Dexpramipexole falls under the category of compounds termed as benzothiazoles, which shows a broad range of biological activity. As per studies conducted in preclinical models, dexpramipexole has demonstrated its neuroprotective activity in CNS to be dependent on the function of mitochondrial (Alavian et al., 2012), including the improvement in survivability of SOD1G93A mouse model (Bennett et al., 2014). However, this compound was not capable to exhibit its therapeutic effects in ALS (Cudkowiczetal., 2013).
Combining nano-differential scanning fluorimetry and microscale thermophoresis to investigate VDAC1 interaction with small molecules
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Hubert Gorny, Angélique Mularoni, Jean-Guy Delcros, Céline Freton, Jordane Preto, Isabelle Krimm
E. coli BL21 were purchased from Invitrogen. Plasmid pET-21A was purchased from Novagen. pDNR-LIR-hVDAC was purchased from Dharmacon. Ampicillin, IPTG, Triton 100X, Guanidine hydrochloride, Acrylamide: Bisacrylamide 37.5:1, SDS 10%, Temed, APS, TGS 10X, NH4Cl and CaCl2 were purchased from Euromedex. NaCl, NaH2PO4, K2HPO4, KH2PO4, glucose, LB-broth, Tris-HCl, NADH, propofol, quinidine, ubiquinone 0, Laemli 6X, β-mercaptoethanol, PBS, Na2HPO4, K2SO4 and metformin were purchased from ThermoFisher. Aspirin, catechin, curcumin, DCCD, DPC, emodin, fluoxetine, and MnCl2 were purchased from Fluorochem. Imidazole, DIDS, DMSO, ReadyBlue Protein Gel stain, EDTA, MgCl2, CoCl2, H2BO3, acetone and ethanol were purchased from Sigma-Aldrich. FeSO4 and ZnSo4 were purchased from Biobasic. CuCl2 and Mo7O24 were purchased from Roth. 15NH4Cl, D2O and deuterated glucose were purchased from Innova-Chem. LDAO was purchased from CliniSciences. Itraconazole was purchased from Cayman Chemical company. VBIT4 was purchased from Aobious. Cannabidiol was purchased from Carbosynth. Olesoxime was obtained from in-house chemical library.
A blend containing docosahexaenoic acid, arachidonic acid, vitamin B12, vitamin B9, iron and sphingomyelin promotes myelination in an in vitro model
Published in Nutritional Neuroscience, 2020
Jonas Hauser, Sébastien Sultan, Andreas Rytz, Pascal Steiner, Nora Schneider
Cells were seeded on the same 96 well plate and were treated with a blend of DHA, ARA, vit B12, vit B9, Fe and SM. All nutrients were used at the same concentrations as in experiment 1. Treatment with Olesoxime (300nM) was used as a positive control (TRO 19622, 300nM, Sigma, 22033-87-0, dissolved in DMSO final concentration 0.018%) [35]. Blend and Olesoxime treated wells were compared to non-treated control wells (non-supplemented culture medium). Six wells were seeded for each condition on the same 96 well plate.