Oxidative stress and reduced antioxidant defenses in peripheral cells from familial Alzheimer’s patients

Cecchi, Cristina; Fiorillo, Claudia; Sorbi, Sandro; Latorraca, Stefania; Nacmias, Benedetta; Bagnoli, Silvia; Nassi, Paolo; Liguri, Gianfranco

doi:10.1016/s0891-5849(02)01049-3

Cited by 144 publications

(95 citation statements)

References 45 publications

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“…Our previous report found a clear increase in free radicalmediated injury to DNA in FAD fibroblasts relative to healthy controls [15]. In the present study, the observed enrichment of histone-associated oligonucleosomes released to the cytoplasm suggests a greater increase in DNA fragmentation in APPV717I and PS-1 fibroblasts exposed to prefibrillar A␤ 1-42 aggregates than in wild-type cells ( Table 2).…”

Section: Apoptotic Markerssupporting

confidence: 67%

“…It is well known that oxidative stress can be caused by increased free radical production and/or weakening of cellular antioxidant defences, which include antioxidant enzymes, lipophilic and hydrophilic scavengers. We have recently found that lymphoblasts and fibroblasts from FAD patients with APPV717I and PS-1 gene mutations had lower basal TAC than healthy controls [15,16]. In the present study, we measured the change in non-enzymatic, hydrophilic TAC, relating it to the effect of differing amyloid species.…”

Section: Oxidative Stressmentioning

confidence: 87%

“…We previously reported a clear increase in membrane lipoperoxidation level in peripheral cells from FAD patients compared to age-matched healthy subjects [15]. Here, we investigate whether the oxidativedamaged membranes of APPV717I fibroblasts enhance the adsorption of the amyloid assemblies on the cellular surfaces.…”

Section: Amyloid Aggregates Penetrate Into Fibroblastsmentioning

confidence: 89%

“…However, studies of autopsied brain tissue cannot clarify whether abnormal oxidative processes are inherent properties of AD cells or are secondary to neurodegeneration. Since our previous results showed a marked increase in oxidation levels of lipids and proteins in peripheral cells from some FAD patients [15], we investigated whether these early modifications could influence the aggregation rate of amyloid assemblies and the translocation process by which the amyloid assemblies appear inside the fibroblasts. Under our experimental conditions, A␤ 1-40 and A␤ 1-42 aggregates are characterized by an extensive ␤-sheet structure able to bind ThT and are endowed with typical morphological features of prefibrillar and fibrillar aggregates.…”

Section: Discussionmentioning

confidence: 99%

“…Many recent investigations have strengthened the hypothesis that an impairment in cellular total antioxidant capacity (TAC) plays a central role in AD [47,46]. Recently, we have found that lymphoblasts and fibroblasts carrying APP and PS-1 gene mutations have a significant TAC impairment compared to healthy controls [15].…”

Section: Introductionmentioning

confidence: 86%

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Increased susceptibility to amyloid toxicity in familial Alzheimer's fibroblasts

Cecchi

Fiorillo

Baglioni

et al. 2007

Neurobiology of Aging

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Much experimental evidence suggests that an imbalance in cellular redox status is a major factor in the pathogenesis of Alzheimer's disease (AD). Our previous data showed a marked increase in membrane lipoperoxidation in primary fibroblasts from familial AD (FAD) patients. In the present study, we demonstrate that when oligomeric structures of A␤ 1-40 and A␤ 1-42 are added to the culture media, they accumulate quicker near the plasma membrane, and are internalized faster and mostly in APPV717I fibroblasts than in age-matched healthy cells; this results in an earlier and sharper increase in the production of reactive oxygen species (ROS). Higher ROS production leads in turn to an increase in membrane oxidative-injury and significant impairment of cellular antioxidant capacity, giving rise to apoptotic cascade activation and finally to a necrotic outcome. In contrast, healthy fibroblasts appear more resistant to amyloid oxidative-attack, possibly as a result of their plasma membrane integrity and powerful antioxidant capacity. Our data are consistent with increasing evidence that prefibrillar aggregates, compared to mature fibrils, are likely the more toxic species of the peptides. These findings provide compelling evidence that cells bearing increased membrane lipoperoxidation are more susceptible to aggregate toxicity as a result of their reduced ability to counteract amyloid oligomeric attack.

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Section: Apoptotic Markerssupporting

confidence: 67%

Section: Oxidative Stressmentioning

confidence: 87%

Section: Amyloid Aggregates Penetrate Into Fibroblastsmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 86%

See 3 more Smart Citations

Increased susceptibility to amyloid toxicity in familial Alzheimer's fibroblasts

Cecchi

Fiorillo

Baglioni

et al. 2007

Neurobiology of Aging

Self Cite

View full text Add to dashboard Cite

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Developmental Lead Exposure, Epigentics and Late Onset Alzheimer's Disease

Zawia

Basha²

2010

Developmental Neurotoxicology Research

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Microwave‐assisted synthesis of chitosan biguanidine hydrochloride and its antioxidant activity in vitro

Liu

Jin

et al. 2016

J of Applied Polymer Sci

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Chitosan biguanidine hydrochloride (CSGH) was synthesized by guanidinylation of chitosan hydrochloride (CSH) under microwave irradiation and characterized by Fourier transform infrared spectroscopy, gel permeation chromatography, and element analysis. The antioxidant activity of CSGH was evaluated by both chemical and cellular methods. The results showed that CSGH was better than CSH but slightly inferior to ascorbic acid (Vc) for scavenging 2,2‐diphenyl‐1‐picryl‐hydrazyl (DPPH) free radicals, and the DPPH• scavenging ability of CSGH was dose‐dependent. However, cell experiments indicated CSGH had a superior repairing effect on oxidatively damaged cells. The intervention of CSGH could excellently recover the cell morphology, decrease the level of malondialdehyde, and enhance the activity of superoxide dismutase and glutathione peroxidase. CSGH could be a potential antioxidant reagent, and its antioxidant activity was reflected not only in scavenging the free radicals but also in regulating the oxidation/antioxidation balance of damaged cells. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43570.

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Oxidative stress and reduced antioxidant defenses in peripheral cells from familial Alzheimer’s patients

Cited by 144 publications

References 45 publications

Increased susceptibility to amyloid toxicity in familial Alzheimer's fibroblasts

Increased susceptibility to amyloid toxicity in familial Alzheimer's fibroblasts

Developmental Lead Exposure, Epigentics and Late Onset Alzheimer's Disease

Microwave‐assisted synthesis of chitosan biguanidine hydrochloride and its antioxidant activity in vitro

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