Application and Mechanism of Action of a Ketogenic Diet in Antiepileptic Therapy.

Epilepsy is a chronic neurological disorder caused by abnormal discharges of neurons in the brain, which seriously affects the quality of life of patients. Although there are various drug treatments available, many epilepsy patients still experience seizures with the effect of drugs and develop refractory epilepsy. The ketogenic diet can treat drug-refractory epilepsy by regulating the body's metabolism and can enhance the quality of life by improving their cognition, behavior, and sleep quality.

Targeting the RUNX3-miR-186-3p-DAT-IGF1R axis as a therapeutic strategy in a Parkinson's disease model.

With the increasing age of the population worldwide, the incidence rate of Parkinson's disease (PD) is increasing annually. Currently, the treatment strategy for PD only improves clinical symptoms. No effective treatment strategy can slow down the progression of the disease.

Downregulation of Ambra1 by altered DNA methylation exacerbates dopaminergic neuron damage in a fenpropathrin-induced Parkinson-like mouse model.

Fenpropathrin (Fen), a volatile pyrethroid insecticide, is used widely for agricultural applications and has been reported to increase the risk of Parkinson's disease (PD). However, the molecular basis, underlying mechanisms, and pathophysiology of Fen-exposed Parkinsonism remain unknown. Recent studies have revealed epigenetic mechanisms underlying PD-related pathway regulation, including DNA methylation.

Cath-KP, a novel peptide derived from frog skin, prevents oxidative stress damage in a Parkinson's disease model.

Parkinson's disease (PD) is a neurodegenerative condition that results in dyskinesia, with oxidative stress playing a pivotal role in its progression. Antioxidant peptides may thus present therapeutic potential for PD. In this study, a novel cathelicidin peptide (Cath-KP; GCSGRFCNLFNNRRPGRLTLIHRPGGDKRTSTGLIYV) was identified from the skin of the Asiatic painted frog ( ).

miR-100a-5p-enriched exosomes derived from mesenchymal stem cells enhance the anti-oxidant effect in a Parkinson's disease model via regulation of Nox4/ROS/Nrf2 signaling.

Background: The pathogenesis of Parkinson's disease (PD) has not been fully elucidated, and there are no effective disease-modifying drugs for the treatment of PD. Mesenchymal stem cells have been used to treat several diseases, but are not readily available.

Methods: Here, we used phenotypically uniform trophoblast stage-derived mesenchymal stem cells (T-MSCs) from embryonic stem cells, which are capable of stable production, and their exosomes (T-MSCs-Exo) to explore the molecular mechanisms involved in dopaminergic (DA) neuron protection in PD models using experimental assays (e.

Engineered Selenium/Human Serum Albumin Nanoparticles for Efficient Targeted Treatment of Parkinson's Disease via Oral Gavage.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopamine (DA) neurons in the midbrain substantia nigra pars compacta (SNpc). While existing therapeutic strategies can alleviate PD symptoms, they cannot inhibit DA neuron loss. Herein, a tailor-made human serum albumin (HSA)-based selenium nanosystem (HSA/Se nanoparticles, HSA/Se NPs) to treat PD that can overcome the intestinal epithelial barrier (IEB) and blood-brain barrier (BBB) is described.

Fenpropathrin Induces GLT-1 Ubiquitination and Increases IL-6 Secretion through the Mdm2-p53 Pathway.

Human exposure to fenpropathrin, a widely used pesticide, is linked to Parkinson's-like symptoms in the body. However, a specific pathogenic mechanism is still unclear. This study found that fenpropathrin increased the expression of murine double minute 2 (Mdm2) and reduced the expression of p53.

Functional investigation of SLC1A2 variants associated with epilepsy.

Epilepsy is a common neurological disorder and glutamate excitotoxicity plays a key role in epileptic pathogenesis. Astrocytic glutamate transporter GLT-1 is responsible for preventing excitotoxicity via clearing extracellular accumulated glutamate. Previously, three variants (G82R, L85P, and P289R) in SLC1A2 (encoding GLT-1) have been clinically reported to be associated with epilepsy.

An anti-inflammatory and anti-fibrotic proprietary Chinese medicine nasal spray designated as Allergic Rhinitis Nose Drops (ARND) with potential to prevent SARS-CoV-2 coronavirus infection by targeting RBD (Delta)- angiotensin converting enzyme 2 (ACE2) binding.

Background: Since the outbreak of COVID-19 has resulted in over 313,000,000 confirmed cases of infection and over 5,500,000 deaths, substantial research work has been conducted to discover agents/ vaccines against COVID-19. Undesired adverse effects were observed in clinical practice and common vaccines do not protect the nasal tissue. An increasing volume of direct evidence based on clinical studies of traditional Chinese medicines (TCM) in the treatment of COVID-19 has been reported.

Baicalin Induces a Potent Innate Immune Response to Inhibit Respiratory Syncytial Virus Replication Regulating Viral Non-Structural 1 and Matrix RNA.

Respiratory syncytial virus (RSV) infection is the most frequent cause of hospitalization in pediatric patients. Current systemic treatment and vaccines are not curative and re-infection is often associated with a more drastic incidence of the disease. Baicalin is a flavonoid isolated from with potent anti-viral characteristics, namely against RSV.

A Comparison of Epileptogenic Effect of Status Epilepticus Treated With Diazepam, Midazolam, and Pentobarbital in the Mouse Pilocarpine Model of Epilepsy.

Status epilepticus (SE) is a medical emergency associated with acute severe systemic damage and high mortality. Moreover, symptomatic SE is one of the highest risk factors for epileptogenesis. While the antiepileptic drugs (AEDs) are chosen in favor of acute control of SE, the potential short-term and long-term effects of such AEDs have been ignored in clinics.

The Conformationally Sensitive Spatial Distance Between the TM3-4 Loop and Transmembrane Segment 7 in the Glutamate Transporter Revealed by Paired-Cysteine Mutagenesis.

Excitatory amino acid transporters can maintain extracellular glutamate concentrations lower than neurotoxic levels by transferring neurotransmitters from the synaptic cleft into surrounding glial cells and neurons. Previous work regarding the structural studies of Glt , Glt , excitatory amino acid transporter 1 (EAAT1), EAAT3 and alanine serine cysteine transporter 2 described the transport mechanism of the glutamate transporter in depth. However, much remains unknown about the role of the loop between transmembrane segment 3 and 4 during transport.

Overexpression of miR-132-3p contributes to neuronal protection in in vitro and in vivo models of Alzheimer's disease.

One of the neuropathological hallmarks of Alzheimer's disease (AD) is accumulation and deposition of amyloid-beta (Aβ) plaques in the hippocampus. Recently, microRNAs (miRNAs), have been demonstrated to play an essential role in AD. We have previously demonstrated that miR-132-3p exerts neuroprotection via regulating histone deacetylase 3 (HDAC3) in a mouse model of AD.

Protective Effect of Pre-treatment Against Experimental Cerebral Ischemia Injury via Regulating GSK-3β/HO-1 Pathway.

() a famous formula in traditional Chinese medicine, has been clinically used for centuries for treating cerebral diseases, but the protective effects of pre-treatment with on cerebral ischemia have not yet been reported. The present study aimed to test such protective effects and elucidate the underlying mechanisms on cerebral ischemia in rats by phenotypic approaches (i.e.

MiR-30a-5p Regulates GLT-1 Function via a PKCα-Mediated Ubiquitin Degradation Pathway in a Mouse Model of Parkinson's Disease.

Glutamate excitotoxicity is caused by dysfunctional glutamate transporters and plays an important role in the pathogenesis of Parkinson's disease (PD); however, the mechanisms that underlie the regulation of glutamate transporters in PD are still not fully elucidated. MicroRNAs(miRNA), which are abundant in astrocytes and neurons, have been reported to play key roles in regulating the translation of glutamate-transporter mRNA. In this study, we hypothesized that the miR-30a-5p contributes to the pathogenesis of PD by regulating the ubiquitin-mediated degradation of glutamate transporter 1 (GLT-1).

Effects of α-Synuclein-Associated Post-Translational Modifications in Parkinson's Disease.

α-Synuclein (α-syn), a small highly conserved presynaptic protein containing 140 amino acids, is thought to be the main pathological hallmark in related neurodegenerative disorders. Although the normal function of α-syn is closely involved in the regulation of vesicular neurotransmission in these diseases, the underlying mechanisms of post-translational modifications (PTMs) of α-syn in the pathogenesis of Parkinson's disease (PD) have not been fully characterized. The pathological accumulation of misfolded α-syn has a critical role in PD pathogenesis.

Role of autophagy and oxidative stress to astrocytes in fenpropathrin-induced Parkinson-like damage.

Fenpropathrin is an insecticide that is widely used in agriculture. It remains unknown whether fenpropathrin exposure increases the risk of Parkinson's disease. We found that fenpropathrin increased oxidative stress both in vitro and in vivo.

Critical amino acids in the TM2 of EAAT2 are essential for membrane-bound localization, substrate binding, transporter function and anion currents.

Excitatory amino acid transporter 2 (EAAT2), the gene of which is known as solute carrier family 1 member 2 (SLC1A2), is an important membrane-bound transporter that mediates approximately 90% of the transport and clearance of l-glutamate at synapses in the central nervous system (CNS). Transmembrane domain 2 (TM2) of EAAT2 is close to hairpin loop 2 (HP2) and far away from HP1 in the inward-facing conformation. In the present study, 14 crucial amino acid residues of TM2 were identified via alanine-scanning mutations.

Molecular Mechanisms of Glutamate Toxicity in Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disease, the pathological features of which include the presence of Lewy bodies and the neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta. However, until recently, research on the pathogenesis and treatment of PD have progressed slowly. Glutamate and dopamine are both important central neurotransmitters in mammals.

Conformationally Sensitive Proximity Between the TM3-4 Loop and Hairpin Loop 2 of the Glutamate Transporter EAAT2 Revealed by Paired-Cysteine Mutagenesis.

Excitatory amino acid transporters (EAATs) serve to maintain extracellular neurotransmitter concentrations below neurotoxic levels by transporting glutamate from the synaptic cleft into apposed glia and neurons. Although the crystal structures of the archaeal EAAT homologue from , Glt, and the human glutamate transporter, EAAT1, have been resolved, the transport mechanism of the transmembrane 3-4 (TM3-4) loop and its structural rearrangement during transport have remained poorly understood. In order to explore the spatial position and function of the TM3-4 loop in the transport cycle, we engineered a pair of cysteine residues between the TM3-4 loop and hairpin loop 2 (HP2) in cysteine-less EAAT2 (CL-EAAT2).

Pretreatment of Ascorbic Acid Inhibits MPTP-Induced Astrocytic Oxidative Stress through Suppressing NF-B Signaling.

Astrocytes are a major constituent of the central nervous system (CNS). Astrocytic oxidative stress contributes to the development of Parkinson's disease (PD). Maintaining production of antioxidant and detoxification of reactive oxygen and nitrogen species (ROS/RNS) in astrocytes is critical to prevent PD.

Fenpropathrin induces degeneration of dopaminergic neurons via disruption of the mitochondrial quality control system.

The synthetic pyrethroid derivative, fenpropathrin, is a widely used insecticide. However, a variety of toxic effects in mammals have been reported. In particular, fenpropathrin induces degeneration of dopaminergic neurons and parkinsonism.

Generation of a Novel Mouse Model of Parkinson's Disease via Targeted Knockdown of Glutamate Transporter GLT-1 in the Substantia Nigra.

Parkinson's disease (PD) is a common neurodegenerative disease that is characterized by pathological dopaminergic (DA) neuronal death and α-synuclein aggregation. Glutamate excitotoxicity is a well-established pathogenesis of PD that involves dysfunctional expression of glutamate transporters. Glutamate transporter-1 (GLT-1) is mainly responsible for clearance of glutamate at synapses, including DA synapses.

Environmental enrichment prevents Aβ oligomer-induced synaptic dysfunction through mirna-132 and hdac3 signaling pathways.

As the most common cause of progressive cognitive decline in humans, Alzheimer's disease (AD) has been intensively studied, but the mechanisms underlying its profound synaptic dysfunction remain unclear. Here we confirm that exposing wild-type mice to an enriched environment (EE) facilitates signaling in the hippocampus that promotes long-term potentiation (LTP). Exposing the hippocampus of mice kept in standard housing to soluble Aβ oligomers impairs LTP, but EE can fully prevent this.