Non-canonical pathways associated to Amyloid beta and tau protein dyshomeostasis in Alzheimer's disease: A narrative review.

Alzheimer's Disease (AD) is the most common form of dementia among elderly people. This disease imposes a significant burden on the healthcare system, society, and economy due to the increasing global aging population. Current trials with drugs or bioactive compounds aimed at reducing cerebral Amyloid beta (Aβ) plaques and tau protein neurofibrillary tangles, which are the two main hallmarks of this devastating neurodegenerative disease, have not provided significant results in terms of their neuropathological outcomes nor met the expected clinical end-points.

β-Hexachlorocyclohexane triggers neuroinflammatory activity, epigenetic histone post-translational modifications and cognitive dysfunction.

Persistent organic pollutants (POPs), which encompass pesticides and industrial chemicals widely utilized across the globe, pose a covert threat to human health. β-hexachlorocyclohexane (β-HCH) is an organochlorine pesticide with striking stability, still illegally dumped in many countries, and recognized as responsible for several pathogenetic mechanisms. This study represents a pioneering exploration into the neurotoxic effects induced by the exposure to β-HCH specifically targeting neuronal cells (N2a), microglia (BV-2), and C57BL/6 mice.

Natural deep eutectic solvents protect RNA from thermal-induced degradation.

RNA is a fundamental nucleic acid for life and it plays important roles in the regulation of gene transcription, post-transcriptional regulation, and epigenetic regulation. Recently, the focus on this nucleic acid has significantly increased due to the development of mRNA vaccines and RNA-based gene therapy protocols. Unfortunately, RNA based products show constrains mainly owing to instability and easy degradability of the RNA molecules.

Neuroprotective Effects of PARP Inhibitors in Models of Alzheimer's Disease.

Alzheimer's disease (AD) is an irreversible age-related neurodegenerative disorder clinically characterized by severe memory impairment, language deficits and cognitive decline. The major neuropathological hallmarks of AD include extracellular deposits of the β-amyloid (Aβ) peptides and cytoplasmic neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein. The accumulation of plaques and tangles in the brain triggers a cascade of molecular events that culminate in neuronal damage and cell death.

Effect of Natural Deep Eutectic Solvents on -Resveratrol Photo-Chemical Induced Isomerization and 2,4,6-Trihydroxyphenanthrene Electro-Cyclic Formation.

-Resveratrol is a natural bioactive compound with well-recognized health promoting effects. When exposed to UV light, this compound can undergo a photochemically induced / isomerization and a 6π electrochemical cyclization with the subsequent formation of 2,4,6-trihydroxyphenanthrene (THP). THP is a potentially harmful compound which can exert genotoxic effects.

Pharmacokinetic properties of a novel formulation of S-adenosyl-L-methionine phytate.

S-adenosyl-L-methionine (SAM), the main endogenous methyl donor, is the adenosyl derivative of the amino acid methionine, which displays many important roles in cellular metabolism. It is widely used as a food supplement and in some countries is also marketed as a drug. Its interesting nutraceutical and pharmacological properties prompted us to evaluate the pharmacokinetics of a new form of SAM, the phytate salt.

Fatty Acid Amide Hydrolase (FAAH) Inhibition Modulates Amyloid-Beta-Induced Microglia Polarization.

The ability of endocannabinoid (eCB) to change functional microglial phenotype can be explored as a possible target for therapeutic intervention. Since the inhibition of fatty acid amide hydrolase (FAAH), the main catabolic enzyme of anandamide (AEA), may provide beneficial effects in mice model of Alzheimer's disease (AD)-like pathology, we aimed at determining whether the FAAH inhibitor URB597 might target microglia polarization and alter the cytoskeleton reorganization induced by the amyloid-β peptide (Aβ). The morphological evaluation showed that Aβ treatment increased the surface area of BV-2 cells, which acquired a flat and polygonal morphology.

Hyperexpression of CDRs and HWP1 genes negatively impacts on Candida albicans virulence.

C. albicans is a commensal organism present in the human microbiome of more than 60% of the healthy population. Transition from commensalism to invasive candidiasis may occur after a local or a general failure of host's immune system.

Stimulation of the Serotonin Receptor 7 Restores Brain Histone H3 Acetylation and MeCP2 Corepressor Protein Levels in a Female Mouse Model of Rett Syndrome.

Rett syndrome (RTT) is a rare neurological disorder caused by mutations in the X-linked MECP2 gene, characterized by severe behavioral and physiological impairments for which no cure is available. The stimulation of serotonin receptor 7 (5-HT7R) with its selective agonist LP-211 (0.25 mg/kg/day for 7 days) was proved to rescue neurobehavioral alterations in a mouse model of RTT.

Green Route for the Isolation and Purification of Hyrdoxytyrosol, Tyrosol, Oleacein and Oleocanthal from Extra Virgin Olive Oil.

Extra virgin olive oil (EVOO) phenols represent a significant part of the intake of antioxidants and bioactive compounds in the Mediterranean diet. In particular, hydroxytyrosol (HTyr), tyrosol (Tyr), and the secoiridoids oleacein and oleocanthal play central roles as anti-inflammatory, neuro-protective and anti-cancer agents. These compounds cannot be easily obtained via chemical synthesis, and their isolation and purification from EVOO is cumbersome.

Blueberry Counteracts BV-2 Microglia Morphological and Functional Switch after LPS Challenge.

Microglia, the innate immune cells of the CNS, respond to brain injury by activating and modifying their morphology. Our study arises from the great interest that has been focused on blueberry (BB) for the antioxidant and pharmacological properties displayed by its components. We analyzed the influence of hydroalcoholic BB extract in resting or lipopolysaccharide (LPS)-stimulated microglia BV-2 cells.

Glucagon-Like Peptide-1: A Focus on Neurodegenerative Diseases.

Diabetes mellitus is one of the major risk factors for cognitive dysfunction. The pathogenesis of brain impairment caused by chronic hyperglycemia is complex and includes mitochondrial dysfunction, neuroinflammation, neurotransmitters' alteration, and vascular disease, which lead to cognitive impairment, neurodegeneration, loss of synaptic plasticity, brain aging, and dementia. Glucagon-like peptide-1 (GLP-1), a gut released hormone, is attracting attention as a possible link between metabolic and brain impairment.

Insights into the Phytochemistry of the Cuban Endemic Medicinal Plant : Fideloside, a Novel Bioactive 8--glycosyl 2,3-Dihydroflavonol.

(Phyllanthaceae) is an endemic evergreen tropical plant of Cuba that grows in the western part of the island and is used in traditional medicine as an infusion. The aqueous extract of this plant presents a wide range of pharmacological activitiessuch as antimutagenic, antioxidant and antiviral effects. Given the many beneficial effects and the great interest in the development of new pharmacological products from natural sources, the aim of this work was to investigate the phytochemistry of this species and to elucidate the structure of the main bioactive principles.

Anti-Inflammatory Activity of A Polyphenolic Extract from in In Vitro and In Vivo Models of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder and the primary form of dementia in the elderly. One of the main features of AD is the increase in amyloid-beta (Aβ) peptide production and aggregation, leading to oxidative stress, neuroinflammation and neurodegeneration. Polyphenols are well known for their antioxidant, anti-inflammatory and neuroprotective effects and have been proposed as possible therapeutic agents against AD.

Poly(ADP-ribosylated) proteins in β-amyloid peptide-stimulated microglial cells.

Amyloid-treated microglia prime and sustain neuroinflammatory processes in the central nervous system activating different signalling pathways inside the cells. Since a key role for PARP-1 has been demonstrated in inflammation and in neurodegeneration, we investigated PARylated proteins in resting and in β-amyloid peptide treated BV2 microglial cells. A total of 1158 proteins were identified by mass spectrometry with 117 specifically modified in the amyloid-treated cells.

Behind Resveratrol Stabilization by Carboxymethylated (1,3/1,6)-β-d-Glucan: Does the Polyphenol Play a Role in Polymer Structural Organization?

Resveratrol stability in solution can be improved by combining the polyphenol with carboxymethylated (1,3/1,6)-β-d-glucan (CM-glucan), a carbohydrate polymer widely used in the food and pharmaceutical industries. The present work was undertaken to elucidate the mechanism behind this stabilizing effect. The supramolecular structural, physico-chemical and morphological features of the CM-glucan/resveratrol complex have been studied under different physical and chemical stimuli by means of spectroscopic techniques, microscopy and physical methods such as UV-Visible spectroscopy (UV-Vis), spectrofluorimetry, Circular Dichroism (CD), Infrared spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM).

The Interaction of Hypotaurine and Other Sulfinates with Reactive Oxygen and Nitrogen Species: A Survey of Reaction Mechanisms.

Considerable strides have been made in understanding the oxidative mechanisms involved in the final steps of the cysteine pathway leading to taurine. The oxidation of sulfinates, hypotaurine and cysteine sulfinic acid, to the respective sulfonates, taurine and cysteic acid, has never been associated with any specific enzyme. Conversely, there is strong evidence that in vivo formation of taurine and cysteic acid is the result of sulfinate interaction with a variety of biologically relevant oxidants.

HPLC Determination of Bioactive Sulfur Compounds, Amino Acids and Biogenic Amines in Biological Specimens.

There is an increasing interest for analytical methods aimed to detect biological sulfur-containing amines, because of their involvement in human diseases and metabolic disorders. This work describes an improved HPLC method for the determination of sulfur containing amino acids and amines from different biological matrices. We optimized a pre-column derivatization procedure using dabsyl chloride, in which dabsylated products can be monitored spectrophotometrically at 460 nm.

Poly(ADP-ribosylated) proteins in mononuclear cells from patients with type 2 diabetes identified by proteomic studies.

Aims: In diabetes, hyperglycemia increases reactive oxygen species that induce DNA damage and poly(ADP-ribose)polymerase activation. The aim of this study is to characterize the proteomic profile and the role of poly(ADP-ribosylation) in patients with type 2 diabetes.

Methods: A proteomic platform based on 2DE and MALDI-ToF spectrometry was applied to peripheral blood mononuclear cells obtained from two different cohorts in which diabetic (n = 14) and normoglycemic patients (n = 11) were enrolled.

Bioenergetic Impairment in Animal and Cellular Models of Alzheimer's Disease: PARP-1 Inhibition Rescues Metabolic Dysfunctions.

Amyloid-beta peptide accumulation in the brain is one of the main hallmarks of Alzheimer's disease. The amyloid aggregation process is associated with the generation of free radical species responsible for mitochondrial impairment and DNA damage that in turn activates poly(ADP-ribose)polymerase 1 (PARP-1). PARP-1 catalyzes the poly(ADP-ribosylation), a post-translational modification of proteins, cleaving the substrate NAD+ and transferring the ADP-ribose moieties to the enzyme itself or to an acceptor protein to form branched polymers of ADP-ribose.

Neuroprotective Effect of Brassica oleracea Sprouts Crude Juice in a Cellular Model of Alzheimer's Disease.

Unlabelled: β-Amyloid peptide (Aβ) aberrant production and aggregation are major factors implicated in the pathogenesis of Alzheimer's disease (AD), causing neuronal death via oxidative stress. Several studies have highlighted the importance of polyphenolic antioxidant compounds in the treatment of AD, but complex food matrices, characterized by a different relative content of these phytochemicals, have been neglected. In the present study, we analyzed the protective effect on SH-SY5Y cells treated with the fragment Aβ 25-35 by two crude juices of broccoli sprouts containing different amounts of phenolic compounds as a result of different growth conditions.

PARP-1 involvement in neurodegeneration: A focus on Alzheimer's and Parkinson's diseases.

DNA damage is the prime activator of the enzyme poly(ADP-ribose)polymerase1 (PARP-1) whose overactivation has been proven to be associated with the pathogenesis of numerous central nervous system disorders, such as ischemia, neuroinflammation, and neurodegenerative diseases. Under oxidative stress conditions PARP-1 activity increases, leading to an accumulation of ADP-ribose polymers and NAD(+) depletion, that induces energy crisis and finally cell death. This review aims to explain the contribution of PARP-1 in neurodegenerative diseases, focusing on Alzheimer's and Parkinson's disease, to stimulate further studies on this issue and thereby engage a new perspective regarding the design of possible therapeutic agents or the identification of biomarkers.

β-sheet interfering molecules acting against β-amyloid aggregation and fibrillogenesis.

β-Sheet aggregates and amyloid fibrils rising from conformational changes of proteins are observed in several pathological human conditions. These structures are organized in β-strands that can reciprocally interact by hydrophobic and π-π interactions. The amyloid aggregates can give rise to pathological conditions through complex biochemical mechanisms whose physico-chemical nature has been understood in recent times.

Isolation and identification of 2,4,6-trihydroxyphenanthrene as a byproduct of trans-resveratrol photochemical isomerization and electrocyclization.

UV irradiation of trans-resveratrol leads to its photochemical isomerization and electrocyclization, giving rise to different byproducts. Preliminary attempts to purify and characterize these products were in the majority of cases unsuccessful. In the present work, the resveratrol photoreaction products were analyzed by HPLC, and one of these compounds, 2,4,6-trihydroxyphenanthrene (THP), was purified and unambiguously identified.