Decreased Catalase Activity but Unchanged Superoxide Dismutase Activity in Brains of Patients with Dementia of Alzheimer Type

Gsell, W.; Conrad, Rudolf; Hickethier, Majida; Sofić, E.; Frölich, Lutz; Wichart, Ildiko; Jellinger, K. A.; Moll, Gunther H.; Ransmayr, Gerhard; Beckmann, H.; Riederer, Peter

doi:10.1046/j.1471-4159.1995.64031216.x

Cited by 156 publications

(56 citation statements)

References 27 publications

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“…Several studies have reported the reduction of SOD in the frontal cortex of AD patients (40), whereas a slight elevation of SOD was demonstrated in the caudate nucleus of AD patients (41). Alternatively, other researchers have suggested that no changes in SOD levels are seen in AD brains (42). Recently, Ansari and Scheff (43) reported a strong correlation between oxidative damage levels (total SOD, GSH, catalase, thiobarbituric acid reactive substances, protein carbonyl, 3-nitrotyrosine, 4-hydroxynonenal, and acrolein) and the variable dementia status of subjects.…”

Section: Discussionmentioning

confidence: 99%

SOD1 (Copper/Zinc Superoxide Dismutase) Deficiency Drives Amyloid β Protein Oligomerization and Memory Loss in Mouse Model of Alzheimer Disease

Murakami

Murata

Noda

et al. 2011

Journal of Biological Chemistry

217

179

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Oxidative stress is closely linked to the pathogenesis of neurodegeneration. Soluble amyloid ␤ (A␤) oligomers cause cognitive impairment and synaptic dysfunction in Alzheimer disease (AD). However, the relationship between oligomers, oxidative stress, and their localization during disease progression is uncertain. Our previous study demonstrated that mice deficient in cytoplasmic copper/zinc superoxide dismutase (CuZn-SOD, SOD1) have features of drusen formation, a hallmark of agerelated macular degeneration (Imamura, Y., Noda, S., Hashizume, K., Shinoda, K., Yamaguchi, M., Uchiyama, S., Shimizu, T., Mizushima, Y., Shirasawa, T., and Tsubota, K. (2006) Proc. Natl. Acad. Sci. U.S.A. 103, 11282-11287). Amyloid assembly has been implicated as a common mechanism of plaque and drusen formation. Here, we show that Sod1 deficiency in an amyloid precursor protein-overexpressing mouse model (AD mouse, Tg2576) accelerated A␤ oligomerization and memory impairment as compared with control AD mouse and that these phenomena were basically mediated by oxidative damage. The increased plaque and neuronal inflammation were accompanied by the generation of N ⑀ -carboxymethyl lysine in advanced glycation end products, a rapid marker of oxidative damage, induced by Sod1 gene-dependent reduction. The Sod1 deletion also caused Tau phosphorylation and the lower levels of synaptophysin. Furthermore, the levels of SOD1 were significantly decreased in human AD patients rather than non-AD agematched individuals, but mitochondrial SOD (Mn-SOD, SOD2) and extracellular SOD (CuZn-SOD, SOD3) were not. These findings suggest that cytoplasmic superoxide radical plays a critical role in the pathogenesis of AD. Activation of Sod1 may be a therapeutic strategy for the inhibition of AD progression. Alzheimer disease (AD)3 is characterized by amyloid deposits in senile plaques mainly consisting of 40-and 42-mer amyloid ␤ proteins (A␤40 and A␤42) (1, 2). These proteins are produced from amyloid precursor protein (APP) by ␤-and ␥-secretases. A␤42 plays a more important role in the pathogenesis of AD than A␤40 because of its greater aggregation propensity and higher neurotoxicity (3). It has been well demonstrated that oxidative stress is a contributing factor to neurodegenerative disease progression (4, 5). A␤-induced neurotoxicity has been linked to oxidative stress via protein radicalization in vitro (6, 7). Soluble oligomeric assemblies (50ϳ60 kDa; e.g. A␤-derived diffusible ligand, A␤ * 56, and globulomer) of A␤ rather than insoluble fibrils are believed to inhibit long term potentiation and induce neuronal loss (8, 9).Many defensive systems protect mammals from oxidative stress caused by reactive oxygen species, including superoxide radicals, hydrogen peroxide, hydroxyl radicals, and singlet oxygen. Superoxide dismutase (SOD) is one of the major antioxidant enzymes that catalyzes the conversion of superoxide radicals to hydrogen peroxide (10). SOD consists of three isozymes: copper/zinc SOD (CuZn-SOD, SOD1), which is localized in the cytosol, nucle...

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Section: Discussionmentioning

confidence: 99%

SOD1 (Copper/Zinc Superoxide Dismutase) Deficiency Drives Amyloid β Protein Oligomerization and Memory Loss in Mouse Model of Alzheimer Disease

Murakami

Murata

Noda

et al. 2011

Journal of Biological Chemistry

217

179

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“…Kunz and colleagues showed that SOD activity was increased only in acute phases of BD with no significant difference between euthymic BD and controls [42], which may be linked to a compensatory mechanism in response to ROS overproduction during an acute episode, activating additional mechanisms of neuronal plasticity, such as the anti-oxidative defense systems like SOD [43].…”

Section: Antioxidant Enzymesmentioning

confidence: 99%

Role of oxidative stress in the pathophysiology of bipolar disorder

et al. 2010

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In this work, we review the studies of oxidative stress markers, showing association with the pathophysiology of bipolar disorder (BD). BD is a prevalent, chronic and highly disabling psychiatric disorder. Several hypotheses have been postulated to explain the exact neurochemical mechanisms underlying the pathophysiology of BD, including a role for monoamines, gamma-amino butyric acid (GABA), glutamate, and second messenger singling pathways. More recently, oxidative stress has been implicated in the pathogenesis of BD. Recent studies have reported increased products of lipid peroxidation and alterations of the major antioxidants enzymes in patients with BD. It has been widely demonstrated that the generation of reactive oxygen species (ROS) plays a critical role in the pathophysiology of several neuropsychiatric disorders, such BD.

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“…Accumulation of damaged, oxidized, dysfunctional protein seems to result from a combination of age related increase in the rate of oxygen free radical mediated damage and a loss of the ability to degrade oxidized protein (Facchini et al 2000). Indeed increased levels of oxidized protein and reduced activity of antioxidant enzymes have been demonstrated in the brains of aged individuals with and without AD (Gsell et al 1995;Troni et al 1984), and in diabetes (Table 4).…”

Section: Diabetic Neuropathy-peripheral and Central Nervous Systemmentioning

confidence: 99%

A metabolic and functional overview of brain aging linked to neurological disorders

et al. 2009

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Close correlations have recently been shown among the late onset complications encountered in diabetes and aging linked to neurobiological disorders. Aging in females and males is considered as the end of natural protection against age related diseases like osteoporosis, coronary heart disease, diabetes, Alzheimer's disease and Parkinson's disease, dementia, cognitive dysfunction and hypernatremia. Beside the sex hormones other hormonal changes are also known to occur during aging and many common problems encountered in the aging process can be related to neuroendocrine phenomena. Diabetes mellitus is associated with moderate cognitive deficits and neurophysiologic and structural changes in the brain, a condition that may be referred to as diabetes encephalopathy; diabetes increases the risk of dementia especially in the elderly. The current view is that the diabetic brain features many symptoms that are best described as accelerated brain aging. This review presents and compares biochemical, physiological, electrophysiological, molecular, and pathological data from neuronal tissue of aging and hormone treated control and diabetic animals to arrive at the similarities among the two naturally occuring physiological conditions. Animal models can make a substantial contribution to understanding of the pathogenesis, which share many features with mechanism underlying brain aging. By studying the pathogenesis, targets for pharmacology can be identified, finally leading to delay or prevention of these complications. Antiaging strategies using hormone therapy, chemical and herbal compounds were carried out for reversal of aging effects. Neuronal markers have been presented in this review and similarities in changes were seen among the aging, diabetes and hormone treated (estrogen, DHEA and insulin) brains from these animals. A close correlation was observed in parameters like oxidative stress, enzyme changes, and pathological changes like lipofuscin accumulation in aging and diabetic brain.

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Decreased Catalase Activity but Unchanged Superoxide Dismutase Activity in Brains of Patients with Dementia of Alzheimer Type

Cited by 156 publications

References 27 publications

SOD1 (Copper/Zinc Superoxide Dismutase) Deficiency Drives Amyloid β Protein Oligomerization and Memory Loss in Mouse Model of Alzheimer Disease

SOD1 (Copper/Zinc Superoxide Dismutase) Deficiency Drives Amyloid β Protein Oligomerization and Memory Loss in Mouse Model of Alzheimer Disease

Role of oxidative stress in the pathophysiology of bipolar disorder

A metabolic and functional overview of brain aging linked to neurological disorders

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