A Generalised Increase in Protein Carbonyls in the Brain in Parkinson's but Not Incidental Lewy Body Disease

Abstract

Abstract:The degeneration of neurones in Parkinson's disease (PD) may involve oxidative stress. Previously, increased lipid peroxidation and oxidative DNA damage have been reported in parkinsonian substantia nigra. In the present study the protein carbonyl assay was used to assess oxidative protein damage in postmortem brain tissue from patients with PD and age-matched controls. In brain areas associated with PD, such as substantia nigra, caudate nucleus, and putamen, there was a significant increase in carbonyl levels. However, increased carbonyl levels were also found in areas of the brain not thought to be affected in PD. This perhaps suggests that protein carbonyl formation is related to therapy with L-DOPA, which can exert prooxidant properties in vitro. Consistent with this possibility, brain regions from individuals with incidental Lewy body disease (putative presymptomatic PD) showed no rise in carbonyls in any brain areas. Our data show that either oxidative protein damage occurs widely but late in PD brain, and/or that L-DOPA treatment contributes to protein oxidation.

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

“…ROS, such as O 2 2 and O 2 2 -derived oxidants, may induce oxidative stress in DA neurons and induce and/or exacerbate MPTP neurotoxicity (63). Numerous studies have shown evidence of oxidative stress in PD patients and MPTP-treated mice, including high levels of oxidative nucleic acid damage (64,65) and protein oxidation (5,46). The ROS inducing these molecular modifications are generated by microglial NADPH oxidase and play an important role in the development of oxidative stress in the MPTP model of PD (66).…”

“…Oxidative damage to proteins is significantly increased in the SN of PD patients (46,47) and MPTP mice (5). MPTP-induced protein oxidative damage was assessed by measuring protein carbonylation in the SN.…”

Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

“…Oxidative and nitrative posttranslational modifications have been identified on proteins that may affect the disease progression [81]. This includes increased levels of oxidized protein carbonyls in the SN of PD patients [89,90] and nitration of tyrosine residues within LBs in the PD brain [91,92].…”

Potent induction of total cellular GSH and NQO1 as well as mitochondrial GSH by 3H-1,2-dithiole-3-thione in SH-SY5Y neuroblastoma cells and primary human neurons: Protection against neurocytotoxicity elicited by dopamine, 6-hydroxydopamine, 4-hydroxy-2-nonenal, or hydrogen peroxide

“…Dopaminergic neurons are particularly prone to oxidative and electrophilic stress due to oxidation of dopamine, resulting in the generation of ROS as well as the electrophilic quinone molecules (Spina and Cohen, 1989). ROS-induced alteration of macromolecules including polyunsaturated fatty acids in membrane lipids, proteins, and DNA has been observed in the substantia nigra of the parkinsonian patients and animal models (Alam et al, 1997a;Alam et al, 1997b;Selley, 1998).…”