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Infiltrative Diseases
Published in Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler, Heart Failure, 2023
Other agents that can stabilize TTR include epigallocatechin-3-gallate (EGCG) in green tea, which inhibits amyloid fibril formation, but further evidence is needed.54 AG-10 is a compound that stabilizes wild-type TTR and TTR Val122Ile. A phase II study of 49 patients with ATTR-CM illustrated stabilization of TTR with AG-10,55 and the phase III trial is currently ongoing. Tolcapone, a catechol-O-methyltransferase (COMT) inhibitor used as adjunctive therapy for Parkinson's disease, binds to TTR in human plasma, and stabilizes both wild-type and mutant TTR,56 although studies are still pending.
Introduction to Genomics
Published in Altuna Akalin, Computational Genomics with R, 2020
DNA methylation is usually associated with gene silencing. DNA methyltransferase enzyme catalyzes the addition of a methyl group to cytosine of CpG dinucleotides (while in mammals the addition of methyl group is largely restricted to CpG dinucleotides, methylation can occur in other bases as well). This covalent modification either interferes with transcription factor binding on the region, or methyl-CpG binding proteins induce the spread of repressive chromatin domains, thus the gene is silenced if its promoter has methylated CG dinucleotides. DNA methylation usually occurs in repeat sequences to repress transposable elements. These elements, when active, can jump around and insert them to random parts of the genome, potentially disrupting the genomic functions.
Hormones of the Adrenal Gland
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
Catechol-O-methyltransferase is an extraneuronal enzyme found mainly in the liver and kidney and also in postsynaptic membranes. S-adenosylmethionine is required as a methyl donor, producing normetaphrine from norepinephrine and metaphrine from epinephrine, and 3-methoxy-4-hydroxymandelic acid (also known as vanillylmandelic acid [VMA]) from 3,4-dihydroxymandelic acid.
Safety review of current pharmacotherapies for levodopa-treated patients with Parkinson’s disease
Published in Expert Opinion on Drug Safety, 2023
Angela M Richmond, Kelly E Lyons, Rajesh Pahwa
Another approach is the addition of adjunctive medications with distinct mechanisms of action, such as dopamine agonists (DA), monoamine oxidase-B (MAO-B) inhibitors, catechol-O-methyltransferase (COMT) inhibitors, N-methyl-D-aspartate (NMDA) receptor antagonists, or an adenosine A2A receptor antagonist [32]. In some cases, multiple adjunctive medications are needed for symptomatic relief. Choosing an appropriate adjunctive medication can be challenging. It requires a thorough understanding of additive benefits and potential side effects of the growing list of available PD medications and how these may affect patients who already have distressing motor and non-motor symptoms. Moreover, there is a considerable variety of commercially available PD medications worldwide due to the presence of multiple independent drug regulatory authorities. This narrative review aims to summarize factors to be considered by the US clinician when choosing an adjunctive therapy. The efficacy, safety, and tolerability of current US Federal Drug Administration (FDA)-approved adjunctive therapies for levodopa-treated PD patients experiencing motor complications are evaluated.
A potential paradigm shift in opioid crisis management: The role of pharmacogenomics
Published in The World Journal of Biological Psychiatry, 2022
David Eapen-John, Ayeshah G. Mohiuddin, James L. Kennedy
As mentioned before, dopamine released by VTA neurons into the NAcc reinforces behaviours deemed ‘rewarding’ and produces a feeling of euphoria. Dopamine receptors are classified as D1-like and D2-like. D1-like receptors include DRD1 and DRD5. These receptors increase cAMP and activate the intracellular signalling cascade while the D2-like receptors (DRD2, DRD3, and DRD4), inhibit this process (Jalabert et al. 2011; Zhu et al. 2013; Clarke et al. 2014; Jing Li et al. 2018; Burns et al. 2019). Dopamine levels are regulated in the brain by catechol-O-methyltransferase (COMT) through the degradation of catecholamines including dopamine and norepinephrine. Some studies suggest that DRD1 and DRD2 modulate opioid reinforcement, reward, and opioid-induced neuroadaptation (Clarke et al. 2014; Burns et al. 2019).
DNA methyltransferase inhibitors increase NOD-like receptor activity and expression in a monocytic cell line
Published in Immunopharmacology and Immunotoxicology, 2022
Claire L. Feerick, Declan P. McKernan
DNA methylation and histone acetylation are the best-characterized contributors to the epigenome [17,18] and so are investigated here. DNA methylation, catalyzed by DNA methyltransferase enzymes, involves the addition of a methyl group onto cytosine residues, forming 5-methylcytosine [19]. It is generally accepted that methylation of cytosines in CpG dinucleotides-rich regions, referred to as ‘CpG islands,’ within the transcriptional start sites (TSSs) silences the downstream gene [17]. Histone acetylation is the addition of acetyl groups to lysine residues in histone proteins thereby neutralizing lysine’s positive charge, reducing their affinity for surrounding DNA, and thereby relaxing the chromatin and accommodating expression of underlying genes [20]. Histone acetylation status is maintained by a balance in the activity of two enzymes; histone acetyltransferases (HATs) and histone deacetylases (HDACs) [21]. Drugs targeting epigenetic modifying enzymes have recently been used in the treatment of certain cancers but the full extent of their effects have not been studied [22–26]. Previous work from our group has shown that pharmacological and genetic inhibition of such enzymes affected TLR responses in intestinal epithelial cells [27]. We hypothesized that drugs targeting epigenetic modifications may regulate NOD1/2 expression and pro-inflammatory activity in a monocytic cell line.