Neuronal Cell Rearrangement During Aging: Antioxidant Compounds as a Potential Therapeutic Approach.

Aging is a natural process that leads to time-related changes and a decrease in cognitive abilities, executive functions, and attention. In neuronal aging, brain cells struggle to respond to oxidative stress. The structure, function, and survival of neurons can be mediated by different pathways that are sensitive to oxidative stress and age-related low-energy states.

TNFα-CXCR1/2 partners in crime in insulin resistance conditions.

Type 2 diabetes mellitus (T2D) is defined by chronic hyperglycemia due to insufficient insulin secretion or activity and decreased insulin sensitivity, known as insulin resistance (IR). This condition leads to oxidative stress and inflammation, increasing the risk of systemic inflammatory diseases. Obesity and a sedentary lifestyle are major risk factors for IR and T2D.

Oxidative Stress and Neurodegeneration: Insights and Therapeutic Strategies for Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative condition marked by the gradual deterioration of dopaminergic neurons in the . Oxidative stress has been identified as a key player in the development of PD in recent studies. In the first part, we discuss the sources of oxidative stress in PD, including mitochondrial dysfunction, dopamine metabolism, and neuroinflammation.

Brain Organoids: A Game-Changer for Drug Testing.

Neurological disorders are the second cause of death and the leading cause of disability worldwide. Unfortunately, no cure exists for these disorders, but the actual therapies are only able to ameliorate people's quality of life. Thus, there is an urgent need to test potential therapeutic approaches.

Organoids Modeling Stroke in a Petri Dish.

Stroke is a common neurological disorder, the second leading cause of death, and the third leading cause of disability. Unfortunately, the only approved drug for it is tissue plasminogen, but the therapeutic window is limited. In this context, preclinical studies are relevant to better dissect the underlying mechanisms of stroke and for the drug screening of potential therapies.

Molecular and Cellular Involvement in CIPN.

Many anti-cancer drugs, such as taxanes, platinum compounds, vinca alkaloids, and proteasome inhibitors, can cause chemotherapy-induced peripheral neuropathy (CIPN). CIPN is a frequent and harmful side effect that affects the sensory, motor, and autonomic nerves, leading to pain, numbness, tingling, weakness, and reduced quality of life. The causes of CIPN are not fully known, but they involve direct nerve damage, oxidative stress, inflammation, DNA damage, microtubule dysfunction, and altered ion channel activity.

Therapeutic potential of saffron in brain disorders: From bench to bedside.

Saffron is a spice derived from the flower of Crocus sativus L., which has been used for centuries as a coloring and flavoring agent, as well as a source of medicinal compounds. Saffron contains various bioactive constituents, such as crocin, crocetin, safranal, picrocrocin, and kaempferol, that have shown potential benefits for human health.

Therapeutic advances in neural regeneration for Huntington's disease.

Huntington's disease is a neurodegenerative disease caused by the expansion mutation of a cytosine-adenine-guanine triplet in the exon 1 of the HTT gene which is responsible for the production of the huntingtin (Htt) protein. In physiological conditions, Htt is involved in many cellular processes such as cell signaling, transcriptional regulation, energy metabolism regulation, DNA maintenance, axonal trafficking, and antiapoptotic activity. When the genetic alteration is present, the production of a mutant version of Htt (mHtt) occurs, which is characterized by a plethora of pathogenic activities that, finally, lead to cell death.

Intranasal delivery of NGF rescues hearing impairment in aged SAMP8 mice.

Hearing loss impacts the quality of life and affects communication resulting in social isolation and reduced well-being. Despite its impact on society and economy, no therapies for age-related hearing loss are available so far. Loss of mechanosensory hair cells of the cochlea is a common event of hearing loss in humans.

Probing Gut Participation in Parkinson's Disease Pathology and Treatment via Stem Cell Therapy.

Accumulating evidence suggests the critical role of the gut-brain axis (GBA) in Parkinson's disease (PD) pathology and treatment. Recently, stem cell transplantation in transgenic PD mice further implicated the GBA's contribution to the therapeutic effects of transplanted stem cells. In particular, intravenous transplantation of human umbilical-cord-blood-derived stem/progenitor cells and plasma reduced motor deficits, improved nigral dopaminergic neuronal survival, and dampened α-synuclein and inflammatory-relevant microbiota and cytokines in both the gut and brain of mouse and rat PD models.

Neuroprotective effects of the PPARβ/δ antagonist GSK0660 in in vitro and in vivo Parkinson's disease models.

Background: The underlying mechanism of Parkinson's disease are still unidentified, but excitotoxicity, oxidative stress, and neuroinflammation are considered key actors. Proliferator activated receptors (PPARs) are transcription factors involved in the control of numerous pathways. Specifically, PPARβ/δ is recognized as an oxidative stress sensor, and we have previously reported that it plays a detrimental role in neurodegeneration.

Ketoprofen, lysine and gabapentin co-crystal magnifies synergistic efficacy and tolerability of the constituent drugs: Pre-clinical evidences towards an innovative therapeutic approach for neuroinflammatory pain.

Chronic pain is an enormous public health concern, and its treatment is still an unmet medical need. Starting from data highlighting the promising effects of some nonsteroidal anti-inflammatory drugs in combination with gabapentin in pain treatment, we sought to combine ketoprofen lysine salt (KLS) and gabapentin to obtain an effective multimodal therapeutic approach for chronic pain. Using relevant in vitro models, we first demonstrated that KLS and gabapentin have supra-additive effects in modulating key pathways in neuropathic pain and gastric mucosal damage.

Cell Rearrangement and Oxidant/Antioxidant Imbalance in Huntington's Disease.

Huntington's Disease (HD) is a hereditary neurodegenerative disorder caused by the expansion of a CAG triplet repeat in the gene, resulting in the production of an aberrant huntingtin (Htt) protein. The mutant protein accumulation is responsible for neuronal dysfunction and cell death. This is due to the involvement of oxidative damage, excitotoxicity, inflammation, and mitochondrial impairment.

Differential Effects of Nonsteroidal Anti-Inflammatory Drugs in an In Vitro Model of Human Leaky Gut.

The intestinal barrier is the main contributor to gut homeostasis. Perturbations of the intestinal epithelium or supporting factors can lead to the development of intestinal hyperpermeability, termed "leaky gut". A leaky gut is characterized by loss of epithelial integrity and reduced function of the gut barrier, and is associated with prolonged use of Non-Steroidal Anti-Inflammatories.

Neurotrophic factor-based pharmacological approaches in neurological disorders.

Aging is a physiological event dependent on multiple pathways that are linked to lifespan and processes leading to cognitive decline. This process represents the major risk factor for aging-related diseases such as Alzheimer's disease, Parkinson's disease, and ischemic stroke. The incidence of all these pathologies increases exponentially with age.

The SARS-CoV-2 spike protein binds and modulates estrogen receptors.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein binds angiotensin-converting enzyme 2 as its primary infection mechanism. Interactions between S and endogenous proteins occur after infection but are not well understood. We profiled binding of S against >9000 human proteins and found an interaction between S and human estrogen receptor α (ERα).

Enhancing oxidative phosphorylation over glycolysis for energy production in cultured mesenchymal stem cells.

Objective: Strokes represent as one of the leading causes of death and disability in the USA, however, there is no optimal treatment to reduce the occurrence or improve prognosis. Preconditioning of tissues triggers ischemic tolerance, a physiological state that may involve a metabolic switch (i.e.

Metabolic Switching of Cultured Mesenchymal Stem Cells Creates Super Mitochondria in Rescuing Ischemic Neurons.

Transfer of healthy mitochondria from mesenchymal stem cells (MSCs) to ischemic neurons represents a potent stroke therapeutic. MSCs were grown under ambient conditions (nMSCs) or a metabolic switching paradigm by alternating galactose and glucose in medium (sMSCs) and then assayed for oxygen consumption rates using the Seahorse technology. Subsequently, primary neurons were subjected to oxygen glucose deprivation (OGD) and then co-cultured with either nMSCs or sMSCs.

The SARS-CoV-2 spike protein binds and modulates estrogen receptors.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein binds angiotensin-converting enzyme 2 (ACE2) at the cell surface, which constitutes the primary mechanism driving SARS-CoV-2 infection. Molecular interactions between the transduced S and endogenous proteins likely occur post-infection, but such interactions are not well understood. We used an unbiased primary screen to profile the binding of full-length S against >9,000 human proteins and found significant S-host protein interactions, including one between S and human estrogen receptor alpha (ERα).

Paclitaxel binds and activates C5aR1: A new potential therapeutic target for the prevention of chemotherapy-induced peripheral neuropathy and hypersensitivity reactions.

Chemotherapy-induced peripheral neuropathy (CIPN) and hypersensitivity reactions (HSRs) are among the most frequent and impairing side effects of the antineoplastic agent paclitaxel. Here, we demonstrated that paclitaxel can bind and activate complement component 5a receptor 1 (C5aR1) and that this binding is crucial in the etiology of paclitaxel-induced CIPN and anaphylaxis. Starting from our previous data demonstrating the role of interleukin (IL)-8 in paclitaxel-induced neuronal toxicity, we searched for proteins that activate IL-8 expression and, by using the Exscalate platform for molecular docking simulations, we predicted the high affinity of C5aR1 with paclitaxel.

Inflammation-Independent Antinociceptive Effects of DF2755A, a CXCR1/2 Selective Inhibitor: A New Potential Therapeutic Treatment for Peripheral Neuropathy Associated to Non-Ulcerative Interstitial Cystitis/Bladder Pain Syndrome.

Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a chronic bladder disease of unknown etiology characterized by urinary frequency and episodic and chronic pain. Analgesic treatments for IC/BPS are limited, especially for patients with non-Hunner (non-ulcerative) type IC who usually have poor overall outcomes. Here, we demonstrate that oral treatment with DF2755A, a potent and selective inhibitor of chemokine receptors CXCR1/2, can prevent and reverse peripheral neuropathy associated to non-Hunner IC/BPS by directly inhibiting chemokine-induced excitation of sensory neurons.

Contraceptive drug, Nestorone, enhances stem cell-mediated remodeling of the stroke brain by dampening inflammation and rescuing mitochondria.

Ischemic stroke remains a significant unmet need causing massive mortality and morbidity due to few treatment options with limited therapeutic window. The progestin Nestorone® (segesterone acetate) displays high affinity for the progesterone receptor in exerting its potent birth control and hormone replacement therapy. Accumulating evidence implicates a new utility of Nestorone in affording neuroprotection in a variety of central nervous system diseases, including stroke.

Are We What We Eat? Impact of Diet on the Gut-Brain Axis in Parkinson's Disease.

Parkinson's disease is characterized by motor and non-motor symptoms, such as defects in the gut function, which may occur before the motor symptoms. To date, there are therapies that can improve these symptoms, but there is no cure to avoid the development or exacerbation of this disorder. Dysbiosis of gut microbiota could have a crucial role in the gut-brain axis, which is a bidirectional communication between the central nervous system and the enteric nervous system.

An Update on Graphene-Based Nanomaterials for Neural Growth and Central Nervous System Regeneration.

Thanks to their reduced size, great surface area, and capacity to interact with cells and tissues, nanomaterials present some attractive biological and chemical characteristics with potential uses in the field of biomedical applications. In this context, graphene and its chemical derivatives have been extensively used in many biomedical research areas from drug delivery to bioelectronics and tissue engineering. Graphene-based nanomaterials show excellent optical, mechanical, and biological properties.