Extracellular Self-DNA (esDNA), but Not Heterologous Plant or Insect DNA (etDNA), Induces Plasma Membrane Depolarization and Calcium Signaling in Lima Bean (Phaseolus lunatus) and Maize (Zea mays)

Extracellular self-DNA (esDNA) is produced during cell and tissue damage or degradation and has been shown to induce significant responses in several organisms, including plants. While the inhibitory effects of esDNA have been shown in conspecific individuals, little is known on the early events involved upon plant esDNA perception. We used electrophysiology and confocal laser scanning microscopy calcium localization to evaluate the plasma membrane potential (Vm) variations and the intracellular calcium fluxes, respectively, in Lima bean (Phaseolus lunatus) and maize (Zea mays) plants exposed to esDNA and extracellular heterologous DNA (etDNA) and to etDNA from Spodoptera littoralis larvae and oral secretions. In both species, esDNA induced a significant Vm depolarization and an increased flux of calcium, whereas etDNA was unable to exert any of these early signaling events. These findings confirm the specificity of esDNA to induce plant cell responses and to trigger early signaling events that eventually lead to plant response to damage

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

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