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Treatment duration at this dose typically ranges from 8-12 weeks, followed by an appropriate off-cycle period

138 SIRT5-mediated IDH2 desuccinylation also regulates cellular NADPH homeostasis and redox potential

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Abbreviations 1 H NMR: Proton nuclear magnetic resonance 3-PBLG: 3-Armed poly(-benzyl-l-glutamic acid) 3-PLG: 3-Armed poly(l-glutamic acid) 3-PLG-A-GSH: 3-Armed poly(l-glutamic acid) coupled with alanine and glutathione 3-PLG-dopa: 3-Armed poly(l-glutamic acid) coupled with dopamine 3-PLG-dopa-A-GSH: 3-Armed poly(l-glutamic acid) coupled with dopamine and alanine and glutathione targeting ligands 3-PLG-ibu: 3-Armed poly(l-glutamic acid) coupled with ibuprofen 3-PLG-ibu-A-GSH: 3-Armed poly(l-glutamic acid) coupled with ibuprofen and alanine and glutathione targeting ligands A-GSH: Alanine and glutathione targeting ligands AD: Alzheimer's disease ASCT: Neutral amino acid transporter BBB: Bloodbrain barrier BLG NCA: L-glutamic acid -benzyl ester N -carboxyanhydride BSA: Bovine serum albumin cARLA: 8-(4-Chlorophenylthio)adenosine 3,5-cyclic monophosphate sodium salt + Ro-20-1724 + LiCl + A83-01 CD: -Cyclodextrin CK: Cytokines CNS: Central nervous system CytoD: Cytochalasin D D 2 O: Deuterium oxide DCM: Dichloromethane DIW: Deionized water DMEM: Dulbeccos modified Eagle medium DW: Distilled water EBA: Evans blue-albumin complex EDC/NHS: N -Ethyl- N -(3-(dimethylamino)propyl)carbodiimide/ N -hydroxysuccinimide EG 2 -diamine: 2,2-(Ethylenedioxy)bis(ethylamine) FBS: Fetal bovine serum GLUT-1: Glucose transporter type-1 hEC: Human stem cell-derived endothelial cells IL1-: Interleukin-1 LAT-1: L-type amino acid transporter-1 LRPs: Low density lipoprotein receptor-related proteins NA: Neuraminidase NSAIDs: Non-steroidal anti-inflammatory drugs P app : Apparent permeability coefficient PBS: Phosphate buffered saline PD: Parkinsons disease PDI: Polydispersity index PC: Pericytes PLGA: Poly(lactic- co -glycolic acid) R6G: N -(2-Aminoethyl) rhodamine 6G-amide bis(trifluoroacetate) SF: Sodium fluorescein SLC: Solute carrier SNAT: Small neutral amino acid transporters THF: Tetrahydrofuran TMA-DPH: 1-(4-Trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene TMSI: Trimethylsilyl iodide TNF-: Tumor necrosis factor- References Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ

Contact with the round window membrane is maintained for 30 minutes by placing the animal in a recumbent position Intratympanic injectionEach animal is positioned so that the head is tilted at an angle to favor injection towards the round window niche