Iron Dysregulation in Alzheimer's Disease: LA-ICP-MS Bioimaging of the Distribution of Iron and Ferroportin in the CA1 Region of the Human Hippocampus.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by cognitive decline and neuropathological hallmarks, including β-amyloid (Aβ) plaques, Tau tangles, synaptic dysfunction and neurodegeneration. Emerging evidence suggests that abnormal iron (Fe) metabolism plays a role in AD pathogenesis, but the precise spatial distribution of the Fe and its transporters, such as ferroportin (FPN), within affected brain regions remains poorly understood. This study investigates the distribution of Fe and FPN in the CA1 region of the human hippocampus in AD patients with a micrometer lateral resolution using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS).

Apolipoprotein D as a Potential Biomarker in Neuropsychiatric Disorders.

Neuropsychiatric disorders (NDs) are a diverse group of pathologies, including schizophrenia or bipolar disorders, that directly affect the mental and physical health of those who suffer from them, with an incidence that is increasing worldwide. Most NDs result from a complex interaction of multiple genes and environmental factors such as stress or traumatic events, including the recent Coronavirus Disease (COVID-19) pandemic. In addition to diverse clinical presentations, these diseases are heterogeneous in their pathogenesis, brain regions affected, and clinical symptoms, making diagnosis difficult.

One-way or two-way sweet link between theobromine and depression?

Theobromine is an abundant methylxanthine in cocoa/chocolate. A recent article in BMC Psychiatry concludes that theobromine consumption increases the risk of depression. In our opinion, it is difficult to make a correlation between dietary habits and the risk of depression, the diagnosis of which is not simple to make.

The olfactory Olfr-78/51E2 receptor interacts with the adenosine A receptor. Effect of menthol and 1,8-cineole on A receptor-mediated signaling.

Heteromer formation is unknown for the olfactory family of G protein-coupled receptors (GPCRs). We here identified, in a heterologous system, heteromers formed by the adenosine A receptor (AR), which is a target for neuroprotection, and an olfactory receptor. AR interacts with the receptor family 51, subfamily E, member 2 (OR51E2), the human ortholog of the mouse Olfr-78, whose mRNA is differentially expressed in activated microglia treated with adenosine receptor ligands.

Genetic Inactivation of Free Fatty Acid Receptor 3 Impedes Behavioral Deficits and Pathological Hallmarks in the APP Alzheimer's Disease Mouse Model.

The free fatty acid FFA3 receptor (FFA3R) belongs to the superfamily of G-protein-coupled receptors (GPCRs). In the intestine and adipose tissue, it is involved in the regulation of energy metabolism, but its function in the brain is unknown. We aimed, first, to investigate the expression of the receptor in the hippocampus of Alzheimer disease (AD) patients at different stages of the disease and, second, to assess whether genetic inactivation of the Ffar3 gene could affect the phenotypic features of the APP mouse model.

Antioxidant Supplements versus Health Benefits of Brief/Intermittent Exposure to Potentially Toxic Physical or Chemical Agents.

Although antioxidants can act locally to react with an oxidant, oral administration of "antioxidants" is quite useless in treating oxidative stress in tissues. Furthermore, it does not make sense to consider a vitamin as an antioxidant, but vitamin B3 leads to the in vivo formation of compounds that are essential for reducing this stress. A rigorous treatment of the subject indicates that to deal with oxidative stress, the most direct approach is to enhance the innate antioxidant mechanisms.

Cuprizone-Induced Neurotoxicity in Human Neural Cell Lines Is Mediated by a Reversible Mitochondrial Dysfunction: Relevance for Demyelination Models.

Suitable in vivo and in vitro models are instrumental for the development of new drugs aimed at improving symptoms or progression of multiple sclerosis (MS). The cuprizone (CPZ)-induced murine model has gained momentum in recent decades, aiming to address the demyelination component of the disease. This work aims at assessing the differential cytotoxicity of CPZ in cells of different types and from different species: human oligodendroglial (HOG), human neuroblastoma (SH-SY5Y), human glioblastoma (T-98), and mouse microglial (N-9) cell lines.

Neuroprotective Effect of Apolipoprotein D in Cuprizone-Induced Cell Line Models: A Potential Therapeutic Approach for Multiple Sclerosis and Demyelinating Diseases.

Apolipoprotein D (Apo D) overexpression is a general finding across neurodegenerative conditions so the role of this apolipoprotein in various neuropathologies such as multiple sclerosis (MS) has aroused a great interest in last years. However, its mode of action, as a promising compound for the development of neuroprotective drugs, is unknown. The aim of this work was to address the potential of Apo D to prevent the action of cuprizone (CPZ), a toxin widely used for developing MS models, in oligodendroglial and neuroblastoma cell lines.

Adenosine A and A Receptors Are Able to Interact with Each Other. A Further Piece in the Puzzle of Adenosine Receptor-Mediated Signaling.

The aim of this paper was to check the possible interaction of two of the four purinergic P1 receptors, the A and the A. Discovery of the A-A receptor complex was achieved by means of immunocytochemistry and of bioluminescence resonance energy transfer. The functional properties and heteromer print identification were addressed by combining binding and signaling assays.

Expression of GPR55 and either cannabinoid CB or CB heteroreceptor complexes in the caudate, putamen, and accumbens nuclei of control, parkinsonian, and dyskinetic non-human primates.

Endocannabinoids are neuromodulators acting on specific cannabinoid CB and CB G-protein-coupled receptors (GPCRs), representing potential therapeutic targets for neurodegenerative diseases. Cannabinoids also regulate the activity of GPR55, a recently "deorphanized" GPCR that directly interacts with CB and with CB receptors. Our hypothesis is that these heteromers may be taken as potential targets for Parkinson's disease (PD).

Expression of cannabinoid CB R-GPR55 heteromers in neuronal subtypes of the Macaca fascicularis striatum.

The cannabinoid CB receptor (CB R) is the most abundant G protein-coupled receptor in the central nervous system, consistent with the important role of endocannabinoids as neuromodulators. Cannabinoids also modulate the function of G protein-coupled receptor 55 (GPR55), which forms heteroreceptor complexes with the CB R in the striatum. The aim was to characterize cannabinoid CB R-GPR55 heteromers (CB R/GPR55Hets) in the basal ganglia input nuclei of nonhuman primates, Macaca fascicularis, both in projection neurons and interneurons, by the in situ proximity ligation assay.

Microbiota and Other Preventive Strategies and Non-genetic Risk Factors in Parkinson's Disease.

The exact cause of Parkinson's disease (PD), the second most prevalent neurodegenerative disease in modern societies, is still unknown. Many scientists point out that PD is caused by a complex interaction between different factors. Although the main risk factor is age, there are other influences, genetic and environmental, that individually or in combination may trigger neurodegenerative changes leading to PD.

Antioxidants versus Food Antioxidant Additives and Food Preservatives.

Natural and processed foods are fragile and can become unpalatable and/or rotten. The processed food industry uses preservatives to enable distribution, even to different continents, and to extend the useful life of their products. Preservatives impede oxidation, a mandatory step in rotting, either by aerobic or anaerobic mechanisms.

Hormetic and Mitochondria-Related Mechanisms of Antioxidant Action of Phytochemicals.

Antioxidant action to afford a health benefit or increased well-being may not be directly exerted by quick reduction-oxidation (REDOX) reactions between the antioxidant and the pro-oxidant molecules in a living being. Furthermore, not all flavonoids or polyphenols derived from plants are beneficial. This paper aims at discussing the variety of mechanisms underlying the so-called "antioxidant" action.

Lessons on Differential Neuronal-Death-Vulnerability from Familial Cases of Parkinson's and Alzheimer's Diseases.

The main risk of Alzheimer's disease (AD) and Parkinson's disease (PD), the two most common neurodegenerative pathologies, is aging. In contrast to sporadic cases, whose symptoms appear at >60 years of age, familial PD or familial AD affects younger individuals. Finding early biological markers of these diseases as well as efficacious treatments for both symptom relief and delaying disease progression are of paramount relevance.

Biased receptor functionality versus biased agonism in G-protein-coupled receptors.

Functional selectivity is a property of G-protein-coupled receptors (GPCRs) by which activation by different agonists leads to different signal transduction mechanisms. This phenomenon is also known as biased agonism and has attracted the interest of drug discovery programs in both academy and industry. This relatively recent concept has raised concerns as to the validity and real translational value of the results showing bias; firstly biased agonism may vary significantly depending on the cell type and the experimental constraints, secondly the conformational landscape that leads to biased agonism has not been defined.

Antioxidant Defense Mechanisms in Erythrocytes and in the Central Nervous System.

Differential antioxidant action is found upon comparison of organ/tissue systems in the human body. In erythrocytes (red blood cells), which transport oxygen and carbon dioxide through the circulatory system, the most important issue is to keep hemoglobin in a functional state that requires maintaining the haem group in ferrous (Fe) state. Conversion of oxidized Fe back into Fe in hemoglobin needs a special mechanism involving a tripeptide glutathione, glucose-6-phosphate dehydrogenase, and glucose and NADPH as suppliers of reducing power.

Targeting CB and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson's Disease.

Cannabinoid CB receptors (CBR) and the GPR55 receptor are expressed in striatum and are potential targets in the therapy of Parkinson's disease (PD), one of the most prevalent neurodegenerative diseases in developed countries. The aim of this paper was to address the potential of ligands acting on those receptors to prevent the action of a neurotoxic agent, MPP, that specifically affects neurons of the substantia nigra due to uptake via the dopamine DAT transporter. The SH-SY5Y cell line model was used as it expresses DAT and, therefore, is able to uptake MPP that inhibits complex I of the respiratory mitochondrial chain and leads to cell death.

Expression Pattern of Myelin-Related Apolipoprotein D in Human Multiple Sclerosis Lesions.

Apolipoprotein D (Apo D) is a key molecule in the lipid transport during homeostasis and repair processes in normal and pathological conditions of the nervous system with a putative neuroprotective effect. In the last decades, huge experimental efforts have been made to know the exact mechanism of action of Apo D, even though, it remains an open question. In this regard, studies in mammals and flies have suggested that Apo D seems to act through a variety of cellular mechanisms related with its ability to selectively bind different lipid ligands.

Resveratrol and Related Stilbenoids, Nutraceutical/Dietary Complements with Health-Promoting Actions: Industrial Production, Safety, and the Search for Mode of Action.

This paper reviews the potential of stilbenoids as nutraceuticals. Stilbenoid compounds in wine are considered key factors in health-promoting benefits. Resveratrol and resveratrol-related compounds are found in a large diversity of vegetal products.

Maternal imprinting on cognition markers of wild type and transgenic Alzheimer's disease model mice.

The risk of suffering from Alzheimer's disease (AD) is higher in individuals from AD-affected mothers. The purpose of this investigation was to study whether maternal transmission might produce AD-related alterations in progenies of mice that do not have any genotypic alteration. We used cognitively-intact mothers harbouring in heterozygosity the transgene for overexpressing the Swedish double mutant version of the human amyloid precursor protein (hAβPPswe).