SOD-1 inhibits FAS expression in cortex of APP transgenic mice

Chen, Zhiguo; Duan, Rui‐Sheng; LePecheur, Marie; Paly, Evelyne; London, Jacqueline; Zhu, Jian

doi:10.1007/s10495-005-1879-y

Cited by 10 publications

(6 citation statements)

References 27 publications

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“…The more likely explanation for the different results may be the form of A␤ in the infusion solution. A␤ can be very unstable, and the stability and solubility depend on the preparation protocol, time, and presence of carriers, such as HDL in our study (32). Also, the infusion rate and the final concentration of the peptide reaching different brain structures may easily vary from one laboratory to another.…”

Section: Discussionmentioning

confidence: 91%

“…However, the reduced SOD1 activity in A␤-infused mice reflects a slightly compromised antioxidant defense system, suggesting that A␤-induced oxidative stress may contribute to the learning deficits before clear neuroinflammation is triggered. Many studies suggest that oxidative stress plays a role in early AD and A␤ 1-42 -induced learning deficits (22,(32)(33)(34)(35)(36)(37) and proteomic analyses have demonstrated oxidative damage of brain proteins in advanced stages of AD (40,41). Also, the susceptibility of the brain to lipid peroxidation increases with aging (42).…”

Section: Discussionmentioning

confidence: 99%

“…Oxidative stress is implicated in AD pathology, and in several models of AD, alterations in markers of oxidative stress, including SOD1 and glutathione, have been observed (32)(33)(34)(35)(36)(37). Moreover, oxidative stress and A␤-induced neuronal damage are mediated partially by GSK-3␤ in cell culture and some animal models of AD (38,39).…”

Section: Behavioral Testing Mouse Morris Water Maze (Mwm)mentioning

confidence: 99%

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β-Amyloid infusion results in delayed and age-dependent learning deficits without role of inflammation or β-amyloid deposits

Malm¹,

Ort

Tähtivaara

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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␤-Amyloid (A␤) polypeptide plays a critical role in the pathogenesis of Alzheimer's disease (AD), which is characterized by progressive decline of cognitive functions, formation of A␤ deposits and neurofibrillary tangles, and loss of neurons. Increased genetic production or direct intracerebral administration of A␤ in animal models results in A␤ deposition, gliosis, and impaired cognitive functions. Whether aging renders the brain prone to A␤ and whether inflammation is required for A␤-induced learning deficits is unclear. We show that intraventricular infusion of A␤ 1-42 results in learning deficits in 9-month-old but not 2.5-month-old mice. Deficits that become detectable 12 weeks after the infusion are associated with a slight reduction in Cu,Zn superoxide dismutase activity but do not correlate with A␤ deposition and are not associated with gliosis. In rats, A␤ infusion induced learning deficits that were detectable 6 months after the infusion. Approximately 20% of the A␤ immunoreactivity in rats was associated with astrocytes. NMR spectrum analysis of the animals cerebrospinal fluid revealed a strong reduction trend in several metabolites in A␤-infused rats, including lactate and myo-inositol, supporting the idea of dysfunctional astrocytes. Even a subtle increase in brain A␤ 1-42 concentration may disrupt normal metabolism of astrocytes, resulting in altered neuronal functions and age-related development of learning deficits independent of A␤ deposition and inflammation.aging ͉ cerebrospinal fluid ͉ learning ͉ oxidative stress ͉ Alzheimer's disease A lzheimer's disease (AD) is the most common cause of progressive impairment of cognitive functions in humans during aging (1). Diagnosis is confirmed by the presence of neurofibrillary tangles (formed via hyperphosphorylation of tau) and ␤-amyloid (A␤)-containing plaques (2). A␤, a 39-to 43-aalong polypeptide derived from the A␤ precursor protein (APP), is neurotoxic and plays a critical role in the pathogenesis of AD (1, 2). Mutations in APP or presenilin genes that lead to the elevation of fibrillogenic form of A␤ are responsible for only a small portion of AD cases (1,3,4). In addition, triplication of APP gene-containing chromosome 21 in Down's syndrome results in AD, and the transgenic (TG) mouse models (5) overexpressing human mutant APP or presenilin genes severalfold, show progressive accumulation of A␤ deposits, gliosis, and cognitive decline (2). The relationship between A␤ deposition and cognitive decline is unclear because the severity of dementia does not correlate with A␤ plaques (6). In TG models, cognitive deficits can occur in the absence of A␤ deposits (7-10). Recent findings emphasize the role of soluble A␤ oligomers. A␤ oligomers are highly neurotoxic (11), and their amount in the brain correlates with the severity of AD and with spatial learning deficits in APP TG mice (12). However, it is not completely clear whether the neuropathology in these mice is solely a consequence of A␤ accumulation or whether increased concentrations of other cle...

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Behavioral Testing Mouse Morris Water Maze (Mwm)mentioning

confidence: 99%

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β-Amyloid infusion results in delayed and age-dependent learning deficits without role of inflammation or β-amyloid deposits

Malm¹,

Ort

Tähtivaara

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…8). Nevertheless, the enhancer activity of SOD1 in Drosophila was unexpected because previous studies in a mouse model of AD showed that SOD1 knockdown caused increased activation of apoptotic pathways (Chen et al. , 2005).…”

Section: Discussionmentioning

confidence: 99%

Fenton chemistry and oxidative stress mediate the toxicity of the β‐amyloid peptide in a Drosophila model of Alzheimer’s disease

Rival

Page

Chandraratna

et al. 2009

Eur J of Neuroscience

165

143

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The mechanism by which aggregates of the β-amyloid peptide (Aβ) mediate their toxicity is uncertain. We show here that the expression of the 42-amino-acid isoform of Aβ (Aβ1–42) changes the expression of genes involved in oxidative stress in a Drosophila model of Alzheimer’s disease. A subsequent genetic screen confirmed the importance of oxidative stress and a molecular dissection of the steps in the cellular metabolism of reactive oxygen species revealed that the iron-binding protein ferritin and the H2O2 scavenger catalase are the most potent suppressors of the toxicity of wild-type and Arctic (E22G) Aβ1–42. Likewise, treatment with the iron-binding compound clioquinol increased the lifespan of flies expressing Arctic Aβ1–42. The effect of iron appears to be mediated by oxidative stress as ferritin heavy chain co-expression reduced carbonyl levels in Aβ1–42 flies by 65% and restored the survival and locomotion function to normal. This was achieved despite the presence of elevated levels of the Aβ1–42. Taken together, our data show that oxidative stress, probably mediated by the hydroxyl radical and generated by the Fenton reaction, is essential for Aβ1–42 toxicity in vivo and provide strong support for Alzheimer’s disease therapies based on metal chelation.

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“…FASLG expression was particularly elevated in senile plaques and neurofilament-positive dystrophic neuritis. Transgenic mice overexpressing the wild-type human amyloid precursor protein have been shown to display a much higher expression of FAS 33 . Hyperexpression of FAS mRNA and surface receptors in peripheral T-lymophocytes in AD patients 34 , upregulation of FAS mRNA expression in brains of AD patients 35 , and significantly higher levels of FAS in the cerebrospinal fluid from AD patients compared to controls 36 all support the notion that FAS plays a role in AD related neurodegeneration.…”

Section: Discussionmentioning

confidence: 99%

The FAS gene, brain volume, and disease progression in Alzheimer's disease

Erten-Lyons

Jacobson²,

Kramer

et al. 2009

Alzheimer's & Dementia

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OBJECTIVE To identify single nucleotide polymorphisms (SNPs) that are associated with Alzheimer’s disease (AD) progression and brain volume. METHODS Ninety-seven SNPs were genotyped in 243 subjects from a longitudinal study of healthy aging. Subjects who carried a diagnosis of cognitive impairment (CI) at any study visit (prior to their last visit) and had DNA in the study DNA bank were included. AD progression was defined as the duration from onset of CI to diagnosis of AD. Association of each of the 97 SNPs with AD progression was tested via Cox model. SNPs meeting a nominal significance criterion (p < 0.05) for association with AD progression were reassessed to account for multiple testing by repeating the marker selection process in 10,000 random permutations. Next, the association between the one SNP that survived the multiple-testing adjustment and brain volume was determined by multiple regression analysis in a subgroup of subjects for whom MRI derived brain volume data were available. Brain volumes were adjusted for age at MRI, gender and time from MRI to onset of CI. RESULTS The minor allele of rs1468063 in FAS, member 6 of the tumor necrosis factor receptor superfamily, was significantly associated with faster AD progression after adjustment for multiple testing (Ppermutation=0.049). The same allele in rs1468063 was associated with smaller brain, and larger ventricular volumes (p = 0.02 and 0.04 respectively) CONCLUSION FAS, which plays a role in apoptosis, may be associated with AD by modulating apoptosis and neuronal loss secondary to AD neuropathology.

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SOD-1 inhibits FAS expression in cortex of APP transgenic mice

Cited by 10 publications

References 27 publications

β-Amyloid infusion results in delayed and age-dependent learning deficits without role of inflammation or β-amyloid deposits

β-Amyloid infusion results in delayed and age-dependent learning deficits without role of inflammation or β-amyloid deposits

Fenton chemistry and oxidative stress mediate the toxicity of the β‐amyloid peptide in a Drosophila model of Alzheimer’s disease

The FAS gene, brain volume, and disease progression in Alzheimer's disease

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