Glutathione metabolism and Parkinson's disease

Abstract

It has been established that oxidative stress, defined as the condition in which the sum of free radicals in a cell exceeds the antioxidant capacity of the cell, contributes to the pathogenesis of Parkinson disease. Glutathione is a ubiquitous thiol tripeptide that acts alone or in concert with enzymes within cells to reduce superoxide radicals, hydroxyl radicals, and peroxynitrites. In this review, we examine the synthesis, metabolism, and functional interactions of glutathione and discuss how these relate to the protection of dopaminergic neurons from oxidative damage and its therapeutic potential in Parkinson disease.

Keywords: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 1-methyl-4-phenylpyridinium; 2-oxothiadolazine-4-carboxylate; 3,4-dihydroxyphenylacetic acid; 3-morpholinosydnonimine; 7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine 3-carboxylic acid; ABC; ASK1; ATP-binding cassette transporter; BBB; BSO; COMT; DA; DAT; DHBT-1; DOPAC; GCL; GPX; GSH; GSSG; GST; Glutathione; Glutathione S-transferase; HVA; JNK; LDH; LPS; MDRP; MPP(+); MPTP; N-acetylcysteine; NAC; OTC; Oxidative Stress; P-glycoprotein; PD; Parkinson disease; Parkinson's disease; Pgp; ROS; SIN1; SNpc; Substantia nigra; TH; VMAT2; apoptosis signal-regulating kinase 1; blood–brain barrier; c-Jun N-terminal kinase; catechol-O-methyltransferase; dopamine; dopamine transporter; glutamylcysteine ligase; glutathione; glutathione S-transferase; glutathione disulfide; glutathione peroxidase; homovanillic acid; l-buthionine-(S,R)-sulfoximine; lactate dehydrogenase; lipopolysaccharide; multidrug resistance protein; reactive oxygen species; substantia nigra pars compacta; tyrosine hydroxylase; vesicular monoamine transporter 2; γ-glutamyl-N-transpeptidase; γGT.