Raloxifene and Fulvestrant Exert Antioxidant, Anti-Inflammatory, and Antiapoptotic Action Against Haloperidol-Induced Tardive Dyskinesia in Rats via Activation of the GPER1/PI3k/Akt/Nrf2/HO-1 Signaling Pathways.

Tardive Dyskinesia (TD) is a pathological condition mainly arises due to supersensitivity of dopaminergic D2 receptors is often caused by long-term administration of antipsychotic medication that leads to involuntary hyperkinetic movement. Till now, there is no permanent treatment available to cure TD. The present study aimed to investigate the neuroprotective effect of raloxifene and fulvestrant, a selective estrogen receptor modulator (SERM), against haloperidol-induced TD in rats.

ML-based prediction to experimental validation: Development of dihydroquinazoline based multi-potent ligands as anti-Alzheimer's agents.

Alzheimer's disease (AD) is a multifactorial neurological disorder accounting for the cognitive decline in the patients. The disease is linked to numerous pathological factors including hyperactivation of acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B), accumulation of amyloid-beta (Aβ) plaques and neurofibrillary tangles in the brain etc. The single-target medications already available in the market are found to be ineffective and the research focus is shifting towards the development of multitargeting agents.

Role of Fibroblast Growth Factors in Neurological Disorders: Insight into Therapeutic Approaches and Molecular Mechanisms.

In the last few decades, the incidence and progression of neurological disorders have consistently increased, which mainly occur due to environmental pollution, genetic abnormalities, and modern lifestyles. Several case reports suggested that these factors enhanced oxidative stress, mitochondrial dysfunction, inflammation, and apoptosis, leading to neurological disease. The pathophysiology of neurological disorders is still not understood, mainly due to the diversity within affected populations.

Auranofin-loaded chitosan-lipid hybrid nanoparticle protects against rotenone model of Parkinson's disease via modulation of GSK-3β/ Nrf2/HO-1 signaling.

Auranofin (AUF) is a gold-based compound that has demonstrated a wide range of biological effects, such as anti-inflammatory and antibacterial effects. However, the neuronal use of AUF is restricted due to its low bioavailability. Thus, to improve blood brain barrier (BBB) penetration and investigate its antiparkinsonian impact, the researchers developed AUF-loaded hybrid nanoparticles (AUFHNPs).

G-Protein-Coupled Estrogen Receptor 1 (GPER1) Activation Mitigates Haloperidol-Induced Neurotoxicity in SHSY-5Y Cells and Improves Motor Functions in Adult Zebrafish.

Haloperidol (Halo) is a typical antipsychotic medication used to treat schizophrenia, but its long-term treatment causes neurotoxicity, leading to irregular involuntary movements called Tardive Dyskinesia. Raloxifene (Ralo) and fulvestrant (Fulve) are G-protein-coupled estrogen receptor 1 (GPER1) activators and show similar pharmacological properties as identified in 17β-estradiol. It is reported to have anti-oxidant, anti-inflammatory, and anti-apoptotic properties against neurological disorders.

Elucidating the neuroprotective potential of arbutin in 3-NPA induced HD-like pathology: Insights from in silico, in vitro, and in vivo models.

Huntington's disease (HD) is an inherited, hyperkinetic condition manifested by a triad of motor abnormalities, progressive cognitive impairment, and psychiatric disturbances. Oxidative stress has been implicated among other cellular processes in the pathogenesis of HD. Arbutin, a hydroquinone antioxidant, is reportedly neuroprotective in several animal models of neurodegenerative diseases.

Glycyrrhizic Acid Mitigates Haloperidol-Induced Neurotoxicity in SHSY-5Y Cells and Rats Via Activation of PI3k/Akt/Nrf2 Pathways.

Antipsychotic medications are used to treat a psychological condition called 'Schizophrenia'. However, its long-term administration causes irregular involuntary motor movements, targeting the orofacial regions. Glycyrrhizic acid (GA) is a naturally occurring triterpene saponin glycoside obtained from the roots of the Glycyrrhiza glabra (liquorice) plant and well known for its antioxidant, antiapoptotic and neuroprotective abilities.

Design, synthesis and anticancer evaluation of 4-Substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines as dual topoisomerase I and II inhibitors.

In this study, we herein report the design, synthesis, and anticancer assessment of a series of new 4-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines. The synthesis involved key intermediates such as the 2-aminoester derivative, which underwent a series of reactions to produce compounds 7a-7t. The optimized SAr reactions, utilizing microwave irradiation in DMF, led to high yields and efficient preparation of the desired compounds.

Crosstalk between gut-brain axis: unveiling the mysteries of gut ROS in progression of Parkinson's disease.

"Path to a good mood lies through the gut." This statement seems to imply that it has long been believed that the gut is connected with the brain. Research has shown that eating food activates the reward system and releases dopamine (DA), establishing a link between the peripheral and central nervous system.

Mitochondrial targeted antioxidants as potential therapy for huntington's disease.

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expansion in CAG repeat on huntington (Htt) gene, leading to a degeneration of GABAergic medium spiny neurons (MSNs) in the striatum, resulting in the generation of reactive oxygen species, and decrease antioxidant activity. These pathophysiological alterations impair mitochondrial functions, leading to an increase in involuntary hyperkinetic movement. However, researchers investigated the neuroprotective effect of antioxidants using various animal models.

In Vitro and In Vivo Investigations of Chromone Derivatives as Potential Multitarget-Directed Ligands: Cognitive Amelioration Utilizing a Scopolamine-Induced Zebrafish Model.

Alzheimer's disease is a complex neurological disorder linked with multiple pathological hallmarks. The interrelation of therapeutic targets assists in the enhancement of cognitive decline through interference with overall neuronal transmission. We have synthesized and screened various chromone derivatives as potential multitarget-directed ligands for the effective treatment of Alzheimer's disease.

Bacillus Calmette-Guérin Vaccine Attenuates Haloperidol-Induced TD-like Behavioral and Neurochemical Alteration in Experimental Rats.

Tardive dyskinesia (TD) is a hyperkinetic movement disorder that displays unusual involuntary movement along with orofacial dysfunction. It is predominantly associated with the long-term use of antipsychotic medications, particularly typical or first-generation antipsychotic drugs such as haloperidol. Oxidative stress, mitochondrial dysfunction, neuroinflammation, and apoptosis are major pathophysiological mechanisms of TD.

Calcium channelopathies in neurodegenerative disorder: an untold story of RyR and SERCA.

Introduction: Recent neuroscience breakthroughs have shed light on the sophisticated relationship between calcium channelopathies and movement disorders, exposing a previously undiscovered tale focusing on the Ryanodine Receptor (RyR) and the Sarco/Endoplasmic Reticulum Calcium ATPase (SERCA). Calcium signaling mainly orchestrates neural communication, which regulates synaptic transmission and total network activity. It has been determined that RyR play a significant role in managing neuronal functions, most notably in releasing intracellular calcium from the endoplasmic reticulum.

Impact of noscapine on halting the progression of pentylenetetrazole induced kindling epilepsy in mice.

Epilepsy is caused by an excessive recurrent excitatory neuronal firing, characterized by motor, psychomotor, and sensory impairments. Current therapies fail to produce 100% outcomes because of the complexity of the disease, poor diagnosis, and upsurge to drug-resistant epilepsy. The study repurposed the drug 'noscapine' mainly known for its anti-tussive properties.

Animal models of Huntington's disease and their applicability to novel drug discovery and development.

Introduction: Huntington's disease (HD) is a progressive neurodegenerative disorder caused by an expansion in the CAG trinucleotide repeat in huntingtin (Htt) gene. The discovery of the HD-causing gene prompted the creation of new HD animal models, proving that mutations in the HD gene are linked to either loss of function of the wild-type (un-mutated) gene or toxic gain in the function of a mutated gene.

Areas Covered: Animal models of HD have led to an increased understanding of its pathogenesis and resulted in the discovery of new therapeutic targets/drugs.

An Overview of the Pathophysiological Mechanisms of 3-Nitropropionic Acid (3-NPA) as a Neurotoxin in a Huntington's Disease Model and Its Relevance to Drug Discovery and Development.

Animal models are used to better understand the various mechanisms involved in the pathogenesis of diseases and explore potential pathways that will aid in discovering therapeutic targets. 3-Nitropropionic Acid (3-NPA) is a neurotoxin used to induce Huntington's disease (HD)-like symptoms in experimental animals. The 3-NPA is a fungus toxin that impairs the complex II (succinate dehydrogenase) activity of the mitochondria and reduces ATP synthesis, leading to excessive production of free radicals resulting in the degeneration of GABAergic medium spiny neurons (MSNs) in the striatum.

Monkeypox infection: The past, present, and future.

Monkeypox is a zoonotic illness caused by the monkeypox virus (MPXV) that has a similar etiology to smallpox. The first case of monkeypox was reported in Western and Central Africa in 1971, and in 2003, there was an outbreak of monkeypox viruses outside Africa. According to the World Health Organization (WHO) and Center for Disease Control and Prevention (CDC), monkeypox is transmitted through direct contact with infected animals or persons exposed to infectious sores, scabs, or body fluids.

Involvement of the G-Protein-Coupled Estrogen Receptor-1 (GPER) Signaling Pathway in Neurodegenerative Disorders: A Review.

The G-protein-coupled estrogen receptor-1 (GPER) is an extranuclear estrogen receptor that regulates the expression of several downstream signaling pathways with a variety of biological actions including cell migration, proliferation, and apoptosis in different parts of the brain area. It is endogenously activated by estrogen, a steroidal hormone that binds to GPER receptors which help in maintaining cellular homeostasis and neuronal integrity as well as influences neurogenesis. In contrast, neurodegenerative disorders are a big problem for society, and still many people suffer from motor and cognitive impairments.

Neuroprotective efficacy of 4-Hydroxyisoleucine in experimentally induced intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a severe form of brain injury, which is a major cause of mortality in humans. Hydrocephalus and cerebral hematoma lead to severe neurological deficits. A single autologous blood (ALB) injection in rats' brains induces hemorrhage and other conditions that regularly interfere with the standard treatment of several cellular and molecular pathways.

Inhibition of extracellular regulated kinase (ERK)-1/2 signaling pathway in the prevention of ALS: Target inhibitors and influences on neurological dysfunctions.

Cell signal transduction pathways are essential modulators of several physiological and pathological processes in the brain. During overactivation, these signaling processes may lead to disease progression. Abnormal protein kinase activation is associated with several biological dysfunctions that facilitate neurodegeneration under different biological conditions.

Understanding Abnormal c-JNK/p38MAPK Signaling Overactivation Involved in the Progression of Multiple Sclerosis: Possible Therapeutic Targets and Impact on Neurodegenerative Diseases.

Demyelination, immune dysregulation, and neuroinflammation are the most common triggers of motor neuron disorders such as multiple sclerosis (MS). MS is a chronic demyelinating neurodegenerative disease of the central nervous system caused by abnormal immune activation, which causes myelin sheath damage. Cell signal transduction pathways are required for a variety of physiological and pathological processes in the brain.

Nrf2/HO-1 Signaling Activator Acetyl-11-keto-beta Boswellic Acid (AKBA)-Mediated Neuroprotection in Methyl Mercury-Induced Experimental Model of ALS.

Methylmercury (MeHg) is a potent neurotoxin that causes neurotoxicity and neuronal cell death. MeHg exposure also leads to oligodendrocyte destruction, glial cell overactivation, and demyelination of motor neurons in the motor cortex and spinal cord. As a result, MeHg plays an important role in the progression of amyotrophic lateral sclerosis (ALS)-like neurocomplications.