Oxidative Stress and Neurotoxicity

Abstract

There is increasing awareness of the ubiquitous role of oxidative stress in neurodegenerative disease states. A continuing challenge is to be able to distinguish between oxidative changes that occur early in the disease from those that are secondary manifestations of neuronal degeneration. This perspective highlights the role of oxidative stress in Alzheimer's, Parkinson's, and Huntington's diseases, amyotrophic lateral sclerosis, and multiple sclerosis, neurodegenerative and neuroinflammatory disorders where there is evidence for a primary contribution of oxidative stress in neuronal death, as opposed to other diseases where oxidative stress more likely plays a secondary or by-stander role. We begin with a brief review of the biochemistry of oxidative stress as it relates to mechanisms that lead to cell death, and why the central nervous system is particularly susceptible to such mechanisms. Following a review of oxidative stress involvement in individual disease states, some conclusions are provided as to what further research should hope to accomplish in the field.

Effect of combined exposure to lead and decabromodiphenyl ether on neurodevelopment of zebrafish larvae

“…A substantial body of evidence indicates that oxidative stress plays an important role in developmental neurotoxicity (Sayre et al, 2008). In the present study, increase in ROS production was only observed in zebrafish larvae exposed to BDE-209 and Pb in combination.…”

Brain-Penetrant Tetrahydronaphthalene Thromboxane A2-Prostanoid (TP) Receptor Antagonists as Prototype Therapeutics for Alzheimer’s Disease

“…Purification by silica gel preparative TLC using a 2:1 mixture of hexane/AcOEt as eluent furnished the desired compound. 13 ppm. 13 The activity of the TP receptor was measured by quantifying cellular levels of the IP3 metabolite, IP1, using a homogeneous time-resolved fluorescence (HTRF) assay kit (IP-One Tb, Cisbio, Bedford, MA).…”

“…13 ppm. 13 The activity of the TP receptor was measured by quantifying cellular levels of the IP3 metabolite, IP1, using a homogeneous time-resolved fluorescence (HTRF) assay kit (IP-One Tb, Cisbio, Bedford, MA). QBI-HEK 293A (MP Biomedicals, Solon, OH) cells were transfected with human or mouse TP receptor cDNA (α isoforms) that was cloned into the pcDNA5/TO vector (Invitrogen, Carlsbad, CA), and stable transformants were selected.…”

“…11,12 A consequence of Aβ plaque deposition in the AD brain appears to be the onset of oxidative stress, as evidenced by the generation of oxidized lipids. 13,14 These include the F2α-isoprostanes (iPF2α) that result from nonenzymatic lipid peroxidation of arachidonic acid, with elevated iPF2α levels in brain and cerebrospinal fluid of AD patients, as well as in patients with mild cognitive impairment. 15−17 Increased generation of iPF2α has also been reported in the brain of the Tg2576 mouse model of AD, which expresses mutated human APP, with the elevation of these oxidized lipids coinciding with the appearance of Aβ plaque pathology.…”

Functional expression of carnitine/organic cation transporter OCTN1 in mouse brain neurons: Possible involvement in neuronal differentiation

“…It is considered that neurodegeneration owing to oxidative stress is related to the development of various brain diseases, including Alzheimer's, Parkinson's and Huntington's diseases (Sayre et al, 2008;Cassano et al, 2012). OCTN1 may therefore influence the development of neurodegenerative diseases via its role in transporting endogenous antioxidants.…”