Untargeted metabolomics of 3xTg-AD neurotoxic astrocytes.

Alzheimer's disease (AD) is the most common form of dementia, affecting approximately 47 M people worldwide. Histological features and genetic risk factors, among other evidence, supported the amyloid hypothesis of the disease. This neuronocentric paradigm is currently undergoing a shift, considering evidence of the role of other cell types, such as microglia and astrocytes, in disease progression.

Prenylated Flavanone Isolated from Dalea Species as a Potential Multitarget-Neuroprotector in an In Vitro Alzheimer's Disease Mice Model.

Alzheimer's disease (AD) involves a neurodegenerative process that has not yet been prevented, reversed, or stopped. Continuing with the search for natural pharmacological treatments, flavonoids are a family of compounds with proven neuroprotective effects and multi-targeting behavior. The American genus Dalea L.

Molecular Imaging of Monoamine Oxidase A Expression in Highly Aggressive Prostate Cancer: Synthesis and Preclinical Evaluation of Positron Emission Tomography Tracers.

The role of monoamine oxidase A (MAO-A) in the aggressiveness of prostate cancer (PCa) has been established in recent years. The molecular imaging of MAO-A expression could offer a noninvasive tool for the visualization and quantification of highly aggressive PCa. This study reports the synthesis and preclinical evaluation of C- and F-labeled MAO-A inhibitors as positron emission tomography (PET) tracers for proof-of-concept studies in animal models of PCa.

Transcriptomic Analyses of Neurotoxic Astrocytes Derived from Adult Triple Transgenic Alzheimer's Disease Mice.

Neurodegenerative diseases such as Alzheimer's disease have been classically studied from a purely neuronocentric point of view. More recent evidences support the notion that other cell populations are involved in disease progression. In this sense, the possible pathogenic role of glial cells like astrocytes is increasingly being recognized.

Isolation and characterization of neurotoxic astrocytes derived from adult triple transgenic Alzheimer's disease mice.

Alzheimer's disease has been considered mostly as a neuronal pathology, although increasing evidence suggests that glial cells might play a key role in the disease onset and progression. In this sense, astrocytes, with their central role in neuronal metabolism and function, are of great interest for increasing our understanding of the disease. Thus, exploring the morphological and functional changes suffered by astrocytes along the course of this disorder has great therapeutic and diagnostic potential.

A new naphthalene derivative with anti-amyloidogenic activity as potential therapeutic agent for Alzheimer's disease.

The aggregation of β-amyloid peptides is associated to neurodegeneration in Alzheimer's disease (AD) patients. Consequently, the inhibition of both oligomerization and fibrillation of β-amyloid peptides is considered a plausible therapeutic approach for AD. Herein, the synthesis of new naphthalene derivatives and their evaluation as anti-β-amyloidogenic agents are presented.

Neuroprotective effects of prenylated flavanones isolated from Dalea species, in vitro and in silico studies.

Neurodegenerative diseases (NDs) represent a global problem on public health, with a growing incidence as human longevity increases. Currently, although there are palliative strategies available for most of these diseases, there is a lack of effective therapies for their cure. Flavonoids are extensively studied for their multi-target behavior.

Purification, structural elucidation, antioxidant capacity and neuroprotective potential of the main polyphenolic compounds contained in Achyrocline satureioides (Lam) D.C. (Compositae).

Achyrocline satureioides (Lam) D.C (Compositae) is a native medicinal plant of South America traditionally utilized for its anti-inflammatory, sedative and anti-atherosclerotic properties among others. Neuroprotective effects have been reported in vivo and could be associated to its elevated content of flavonoid aglycones.

Structural evidence of quercetin multi-target bioactivity: A reverse virtual screening strategy.

The ubiquitous flavonoid quercetin is broadly recognized for showing diverse biological and health-promoting effects, such as anti-cancer, anti-inflammatory and cytoprotective activities. The therapeutic potential of quercetin and similar compounds for preventing such diverse oxidative stress-related pathologies has been generally attributed to their direct antioxidant properties. Nevertheless, accumulated evidence indicates that quercetin is also able to interact with multiple cellular targets influencing the activity of diverse signaling pathways.

Quercetin in brain diseases: Potential and limits.

Quercetin is a ubiquitous flavonoid present in beverages, food and plants that has been demonstrated to have a role in the prevention of neurodegenerative and cerebrovascular diseases. In neuronal culture, quercetin increases survival against oxidative insults. Antioxidation appears to be a necessary but not sufficient condition for its neuroprotective action and modulation of intracellular signaling and transcription factors, increasing the expression of antioxidant and pro survival proteins and modulating inflammation, appears as important for neuronal protection.

Antioxidant activity, cellular bioavailability, and iron and calcium management of neuroprotective and nonneuroprotective flavones.

Few studies have been undertaken on the relationship of the structure of flavones and neuroprotection. Previously, we described the structural determinants of the neuroprotective activity of some natural flavones in cerebellar granule neurons in culture against an oxidative insult (H2O2). In the present work, we analyzed anti-oxidant activity, cellular iron, and Ca(2+) levels and cellular bioavailability of neuroprotective and nonneuroprotective flavones in the same experimental paradigm.

Neuroprotective actions of flavones and flavonols: mechanisms and relationship to flavonoid structural features.

Epidemiological studies have shown positive preventive action of flavonoids on cardiovascular and neurodegenerative events. Among the six groups in which flavonoids are classified, the flavones and flavonols, based on the backbone of 2-phenylchromen-4-one (2-phenyl-1-benzopyran-4-one) are the most commonly encountered within the families and genera of the higher plants. Numerous studies support a neuroprotective activity of flavones such as luteolin and flavonols such as kaempherol and quercetin in experimental focal ischemia and models of neurodegeneration.

After cellular internalization, quercetin causes Nrf2 nuclear translocation, increases glutathione levels, and prevents neuronal death against an oxidative insult.

In this work we describe the protective effects of quercetin against H(2)O(2) in 24-h-pretreated neuronal cultures. We explored quercetin availability and subcellular fate through the use of HPLC-Diode Array Detection (DAD), epifluorescence, and confocal microscopy. We focused on quercetin modulation of thiol-redox systems by evaluating changes in mitochondrial thioredoxin Trx2, the levels of total glutathione (GSH), and the expression of the gamma-glutamate-cysteine ligase catalytic subunit (GCLC), the rate-limiting enzyme of GSH synthesis, by the use of Western blot, HPLC, and real-time PCR techniques, respectively.

Pretreatment with natural flavones and neuronal cell survival after oxidative stress: a structure-activity relationship study.

Quercetin shows structural features that have been related to the antioxidant potency of flavonoids and also shows neuroprotection in different models of oxidative death. Because only a few studies have focused on the flavonoid structural requirements for neuroprotection, this work evaluated the protective capacity of 13 flavones structurally related to quercetin, isolated from Kenyan plants, to rescue primary cerebellar granule neurons from death induced by a treatment with 24 h of hydrogen peroxide (150 microM). Each flavone (0-100 microM) was applied 24 h prior to the oxidative insult, and neuronal viability was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.

Cytoprotection by neutral fraction of tannat red wine against oxidative stress-induced cell death.

Some of the beneficial effects of the Mediterranean diet on human pathologies have been attributed to red wine polyphenols. It has been postulated that the antioxidant activity of the latter would be also responsible for the cytoprotective capacity of red wine that has been reported in a few papers. Nevertheless, red wine shows a complex composition, and the active fraction is not known yet.

Cell culture protection and in vivo neuroprotective capacity of flavonoids.

Flavonoids are an important group of recognized antioxidants ubiquitous in fruits, vegetables and herbs. There are epidemiological evidences for the stroke-protecting capacity of flavonoids and while the neuroprotective power of complex extracts rich in flavonoids like those of Ginkgo biloba, green tea or lyophilized red wine have been demonstrated in several studies, neuroprotection by individual flavonoids has been poorly studied in vivo. The neuroprotective capacity of individual flavonoids was studied in PC12 cells in culture and in a model of permanent focal ischemia (permanent Middle Cerebral Artery Occlusion - pMCAO).