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GPx and GSTs catalyze the reduction of electrophiles using GSH GST mutations combined with environmental insults correlate with increased PD risk Maintaining GSH levels may provide a therapeutic treatment for PD Abbreviations ABC ATP-binding cassette transporter ASK1 apoptosis signal-regulating kinase 1 BBB Blood Brain Barrier BSO L-buthionine-(S,R)-sulphoximine COMT Catechol-O-methyltransferase DA Dopamine DAT Dopamine transporter DHBT-1 7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid DOPAC 3,4-Dihydroxyphenylacetic acid γGCS γ-glutamylcysteine synthetase γGC γ-glutamylcysteine γGT γ-glutamyl-n-transpeptidase GCL glutamylcysteine ligase GPX Glutathione Peroxidase GSH Glutathione GSSG glutathione disulfide GST Glutathione S-Transferase HVA Homovanillac Acid JNK c-Jun N-terminal kinase LDH Lactate dehydrogenase LPS Lippopolysaccharide MDRP Multidrug Resistance Protein MPP+ 1-methyl-4-phenylpyridinium MPTP 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine MTT mitochondrial pyruvate-dependent 59,5-Dithiobis (2-nitrobenzoic acid) NAC N-acetylcysteine OTC 2-oxothiadolazine-4-carboxylate PD Parkinson’s disease Pgp P-glycoprotein ROS Reactive oxygen species SIN1 3-morpholinosydnonimine SNP Single nucleotide polymorphism SNpc Substantia nigra pars compacta TH Tyrosine hydroxylase VMAT2 Vesicular monoamine transporter 2 Footnotes Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication

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CagriSema Dosing# CagriSema is a fixed-ratio combination in a single pen injector: Once-weekly subcutaneous injection containing both cagrilintide and semaglutide REDEFINE 1: Dose escalation to the maintenance combination dose over several weeks Dosing ratio: Fixed ratio optimized during the phase 2 program Dosing Comparison Table# Side Effects Comparison# Amycretin Side Effects# In the phase 1b/2a trial published in The Lancet, once-weekly subcutaneous amycretin up to 60 mg had a safety and tolerability profile consistent with GLP-1 and amylin agonists