Lipoperoxidation Is Selectively Involved in Progressive Supranuclear Palsy

Abstract

Abstract. Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by extensive neurofibrillary tangle (NFT) formation and neuronal loss in selective neuronal populations. Currently, no clues to the biological events underlying the pathological process have emerged. In Alzheimer disease (AD), which shares with PSP the occurrence of NFTs, advanced glycation end products (AGEs) as well as oxidation adducts have been found to be increased in association with neurofibrillary pathology. The presence and the amount of lipid and protein oxidation markers, as well as of pyrraline and pentosidine, 2 major AGEs, was assessed by biochemical, immunochemical, and immunocytochemical analysis in midbrain tissue from 5 PSP cases, 6 sporadic AD cases, and 6 age-matched control cases. The levels of 4-hydroxynonenal (HNE) and thiobarbituric acid reactive substances (TBARS), 2 major products of lipid peroxidation, were significantly increased by 1.6-fold (p Ͻ 0.04) and 3.9-fold (p Ͻ 0.01), respectively, in PSP compared with control tissues, whereas in AD only TBARS were significantly increased. In PSP tissue the intensity of neuronal HNE immunoreactivity was proportional to the extent of abnormal aggregated protein. The amount of protein oxidation products and AGEs was instead similar in PSP and control tissues. In AD, a higher but not significant level of pyrraline and pentosidine was measured, whereas the level of carbonyl groups was doubled. These findings indicate that in PSP, unlike in AD, lipid peroxidation is selectively associated with NFT formation. The intraneuronal accumulation of toxic aldehydes may contribute to hamper degradation, leading to its aggregation in the PSP specific abnormal filaments.

Levels of 4-Hydroxynonenal and Malondialdehyde Are Increased in Brain of Human Chronic Users of Methamphetamine

“…The concentration of MDA we observed in post mortem brain of normal subjects is similar to that in reports employing the improved TBARS assay coupled to HPLC separation (Hayn et al, 1996;Lyras et al, 1997;Odetti et al, 2000) and in studies using the colorimetric assay based on reactions of the aldehyde to N-methyl-2-phenyl-indole (Yoshida et al, 2000;Schuessel et al, 2004). The brain levels of HNE we obtained (ϳ1 pmol/mg wet tissue) are within the physiological concentration range of HNE in biological tissues or fluids (ϳ1 M; Esterbauer et al, 1991) and also agree with those reported using direct HPLC/UV detection of HNE (Odetti et al, 2000).…”

LX2343 alleviates cognitive impairments in AD model rats by inhibiting oxidative stress-induced neuronal apoptosis and tauopathy

“…On the other hand, tauopathy induces OS [40] . Some OS markers are notably increased in tauopathy, such as malondialdehyde and 4-hydroxynonenal [41][42][43] . The activation of antioxidant defenses is also observed in tauopathy [44,45] .…”

Regulation of Neuronal Glutathione Synthesis

“…Increased levels of nitrotyrosine, a permanent marker of ONOO − attack on proteins, were previously demonstrated in Alzheimer's disease (AD), PD, and amyotrophic lateral sclerosis (ALS) (8). Increased levels of 4-HNE, the most cytotoxic product of lipid peroxidation (10), have also been documented in AD, PD, ALS, and other neurodegenerative diseases (112,113). Aging is a critical factor for GSH homeostasis.…”