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Oxidative stress mediates the pathogenic effect of different Alzheimer's disease risk factors.

Guglielmotto M, Giliberto L, Tamagno E, Tabaton M - Front Aging Neurosci (2010)

Bottom Line: Moreover, OS produces several effects that may contribute to synaptic function and cell death in AD.We and others have shown that the expression and activity of beta-secretase (named BACE1; beta-site APP cleaving enzyme) is increased by oxidant agents and by lipid peroxidation product 4-hydroxynonenal and that there is a significant correlation between BACE1 activity and oxidative markers in sporadic AD.OS results from several cellular insults such as aging, hyperglycemia, hypoxic insults that are all well known risk factors for AD development.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medicine and Oncology, University of Turin Turin, Italy.

ABSTRACT
Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting the elderly population. Mechanistically, the major cause of the disease bases on the altered processing of the amyloid-beta (Abeta) precursor protein (APP), resulting in the accumulation and aggregation of neurotoxic forms of Abeta. Abeta derives from the sequential proteolytic cleavage of the beta- and gamma-secretases on APP. The causes of Abeta accumulation in the common sporadic form of AD are not completely known, but they are likely to include oxidative stress (OS). OS and Abeta are linked to each other since Abeta aggregation induces OS in vivo and in vitro, and oxidant agents increase the production of Abeta. Moreover, OS produces several effects that may contribute to synaptic function and cell death in AD. We and others have shown that the expression and activity of beta-secretase (named BACE1; beta-site APP cleaving enzyme) is increased by oxidant agents and by lipid peroxidation product 4-hydroxynonenal and that there is a significant correlation between BACE1 activity and oxidative markers in sporadic AD. OS results from several cellular insults such as aging, hyperglycemia, hypoxic insults that are all well known risk factors for AD development. Thus, our data strengthen the hypothesis that OS is a basic common pathway of Abeta accumulation, common to different AD risk factors.

No MeSH data available.


Related in: MedlinePlus

Diagram sketching upstream mediators and downstream consequences of oxidative stress in sporadic AD.
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Figure 1: Diagram sketching upstream mediators and downstream consequences of oxidative stress in sporadic AD.

Mentions: It is expected that, taken into account the increase in life expectancy, the population will continuously age in the next years and virtually everybody has a high probability to become demented. Although this correlation is obvious, the molecular details of the link between aging and cognitive decline are not fully understood. The data here reviewed strongly supported the hypothesis that OS could be a basic common pathway of Aβ accumulation, as determined by different age-related risk factors (Figure 1).


Oxidative stress mediates the pathogenic effect of different Alzheimer's disease risk factors.

Guglielmotto M, Giliberto L, Tamagno E, Tabaton M - Front Aging Neurosci (2010)

Diagram sketching upstream mediators and downstream consequences of oxidative stress in sporadic AD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2874401&req=5

Figure 1: Diagram sketching upstream mediators and downstream consequences of oxidative stress in sporadic AD.
Mentions: It is expected that, taken into account the increase in life expectancy, the population will continuously age in the next years and virtually everybody has a high probability to become demented. Although this correlation is obvious, the molecular details of the link between aging and cognitive decline are not fully understood. The data here reviewed strongly supported the hypothesis that OS could be a basic common pathway of Aβ accumulation, as determined by different age-related risk factors (Figure 1).

Bottom Line: Moreover, OS produces several effects that may contribute to synaptic function and cell death in AD.We and others have shown that the expression and activity of beta-secretase (named BACE1; beta-site APP cleaving enzyme) is increased by oxidant agents and by lipid peroxidation product 4-hydroxynonenal and that there is a significant correlation between BACE1 activity and oxidative markers in sporadic AD.OS results from several cellular insults such as aging, hyperglycemia, hypoxic insults that are all well known risk factors for AD development.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medicine and Oncology, University of Turin Turin, Italy.

ABSTRACT
Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting the elderly population. Mechanistically, the major cause of the disease bases on the altered processing of the amyloid-beta (Abeta) precursor protein (APP), resulting in the accumulation and aggregation of neurotoxic forms of Abeta. Abeta derives from the sequential proteolytic cleavage of the beta- and gamma-secretases on APP. The causes of Abeta accumulation in the common sporadic form of AD are not completely known, but they are likely to include oxidative stress (OS). OS and Abeta are linked to each other since Abeta aggregation induces OS in vivo and in vitro, and oxidant agents increase the production of Abeta. Moreover, OS produces several effects that may contribute to synaptic function and cell death in AD. We and others have shown that the expression and activity of beta-secretase (named BACE1; beta-site APP cleaving enzyme) is increased by oxidant agents and by lipid peroxidation product 4-hydroxynonenal and that there is a significant correlation between BACE1 activity and oxidative markers in sporadic AD. OS results from several cellular insults such as aging, hyperglycemia, hypoxic insults that are all well known risk factors for AD development. Thus, our data strengthen the hypothesis that OS is a basic common pathway of Abeta accumulation, common to different AD risk factors.

No MeSH data available.


Related in: MedlinePlus