124 research outputs found
Oxidative Stress Mediates the Pathogenic Effect of Different Alzheimer's Disease Risk Factors
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-β (Aβ) precursor protein (APP), resulting in the accumulation and aggregation of neurotoxic forms of Aβ. Aβ derives from the sequential proteolytic cleavage of the β- and γ-secretases on APP. The causes of Aβ accumulation in the common sporadic form of AD are not completely known, but they are likely to include oxidative stress (OS). OS and Aβ are linked to each other since Aβ aggregation induces OS in vivo and in vitro, and oxidant agents increase the production of Aβ. 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 β-secretase (named BACE1; β-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 Aβ accumulation, common to different AD risk factors
Oxidative Stress and Hypoxia Contribute to Alzheimer's Disease Pathogenesis: Two Sides of the Same Coin
While it is well established that stroke and cerebral hypoperfusion are risk factors for Alzheimer's disease (AD), the molecular link between ischemia/hypoxia and amyloid precursor protein (APP) processing has only been recently established. Here we review the role of the release of reactive oxygen species (ROS) by the mitochondrial electron chain in response to hypoxia, providing evidence that hypoxia fosters the amyloidogenic APP processing through a biphasic mechanism that up-regulates β-secretase activity, which involves an early release of ROS and an activation of HIF-1α
Estrogens Inhibit Amyloid-β-Mediated Paired Helical Filament-Like Conformation of Tau Through Antioxidant Activity and miRNA 218 Regulation in hTau Mice
The Unexpected Role of A\u3b21-42 Monomers in the Pathogenesis of Alzheimer's Disease
Amyloid- (A) has been proposed as a biomarker and a drug target for the therapy of Alzheimer\u2019s disease (AD).
The neurotoxic entity and relevance of each conformational form of A to AD pathology is still under debate; A oligomers
are considered the major killer form of the peptide whereas monomers have been proposed to be involved in physiological
process. Here we reviewed some different effects mediated by monomers and oligomers on mechanisms involved in AD
pathogenesis such as autophagy and tau aggregation. Data reported in this review demonstrate that A monomers could
have a major role in sustaining the pathogenesis of AD and that AD therapy should be focused not only in the removal of
oligomers but also of monomers
Evidence that the Amyloid beta Precursor Protein-intracellular domain lowers the stress threshold of neurons and has a "regulated" transcriptional role
Stroke and amyloid-beta downregulate TREM-2 and Uch-L1 expression that synergistically promote the inflammatory response
Liver AP-1 activation due to carbon tetrachloride is potentiated by 1,2-dibromoethane but is inhibited by alpha-tocopherol or gadolinium chloride.
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