Haploinsufficiency, Dominant Negative, and Gain-of-Function Mechanisms in Epilepsy: Matching Therapeutic Approach to the Pathophysiology
Discussions are illustrated and reinforced with examples from the literature. (Source: Neurotherapeutics)
Source: Neurotherapeutics - October 14, 2021 Category: Neurology Source Type: research

If Thymectomy Reduces the Risk of Progression of Ocular to Generalized Myasthenia Gravis, Who Should Receive it?
AbstractIn this issue of Neurotherapeutics, Li et.al. report a large retrospective study of the beneficial effects of thymectomy on the progression of ocular myasthenia gravis (OMG) to generalized MG (GMG) (Huanhuan et al. in Neurotherapeutics XX,2021). This paper demonstrates a more than 50% reduction in the risk of GMG when a thymectomy was performed on these patients. The authors conclude with the recommendation that well-designed clinical trials be performed to evaluate the potential that thymectomy in OMG reduces the burden of GMG. (Source: Neurotherapeutics)
Source: Neurotherapeutics - October 14, 2021 Category: Neurology Source Type: research

Electrophysiological Biomarkers in Genetic Epilepsies
AbstractPrecision treatments for epilepsy targeting the underlying genetic diagnoses are becoming a reality. Historically, the goal of epilepsy treatments was to reduce seizure frequency. In the era of precision medicine, however, outcomes such as prevention of epilepsy progression or even improvements in cognitive functions are both aspirational targets for any intervention. Developing methods, both in clinical trial design and in novel endpoints, will be necessary for measuring, not only seizures, but also the other neurodevelopmental outcomes that are predicted to be targeted by precision treatments. Biomarkers that qua...
Source: Neurotherapeutics - October 12, 2021 Category: Neurology Source Type: research

Thymectomy and Risk of Generalization in Patients with Ocular Myasthenia Gravis: A Multicenter Retrospective Cohort Study
This study aims to investigate the association between thymectomy and the risk of generalization in patients with ocular myasthenia gravis (MG). Data on patients with ocular MG from seven neurological centers in China were retrospectively reviewed. Ocular MG na ïve to immunotherapy was categorized according to whether thymectomy was performed (thymectomized group vs. nonsurgical group). Patients in the thymectomized group all underwent surgery within 2 years since ocular symptom onset. The main outcome measure was the generalization. The follow-up period was defined from the date of ocular symptom onset to the da...
Source: Neurotherapeutics - October 8, 2021 Category: Neurology Source Type: research

Correction to: Comparative Effectiveness and Tolerability of the Pharmacology of Monoclonal Antibodies Targeting the Calcitonin Gene-Related Peptide and Its Receptor for the Prevention of Chronic Migraine: a Network Meta-analysis of Randomized Controlled Trials
(Source: Neurotherapeutics)
Source: Neurotherapeutics - October 6, 2021 Category: Neurology Source Type: research

KDS2010, a Newly Developed Reversible MAO-B Inhibitor, as an Effective Therapeutic Candidate for Parkinson ’s Disease
AbstractMonoamine oxidase-B (MAO-B) is a well-established therapeutic target for Parkinson ’s disease (PD); however, previous clinical studies on currently available irreversible MAO-B inhibitors have yielded disappointing neuroprotective effects. Here, we tested the therapeutic potential of KDS2010, a recently synthesized potent, selective, and reversible MAO-B inhibitor in multiple an imal models of PD. We designed and synthesized a series of α-aminoamide derivatives and found that derivative KDS2010 exhibited the highest potency, specificity, reversibility, and bioavailability (>  100%). In additio...
Source: Neurotherapeutics - October 5, 2021 Category: Neurology Source Type: research

Neuroprotective Roles of the Adenosine A3 Receptor Agonist AST-004 in Mouse Model of Traumatic Brain Injury
AbstractTraumatic brain injury (TBI) remains one of the greatest public health concerns with increasing morbidity and mortality rates worldwide. Our group reported that stimulation of astrocyte mitochondrial metabolism by P2Y1 receptor agonists significantly reduced cerebral edema and reactive gliosis in a TBI model. Subsequent data on the pharmacokinetics (PK) and rapid metabolism of these compounds suggested that neuroprotection was likely mediated by a metabolite, AST-004, which binding data indicated was an adenosine A3 receptor (A3R) agonist. The neuroprotective efficacy of AST-004 was tested in a control closed corti...
Source: Neurotherapeutics - October 4, 2021 Category: Neurology Source Type: research

Precision Therapy for Epilepsy Related to Brain Malformations
AbstractMalformations of cortical development (MCDs) represent a range of neurodevelopmental disorders that are collectively common causes of developmental delay and epilepsy, especially refractory childhood epilepsy. Initial treatment with antiseizure medications is empiric, and consideration of surgery is the standard of care for eligible patients with medically refractory epilepsy. In the past decade, advances in next generation sequencing technologies have accelerated progress in understanding the genetic etiologies of MCDs, and precision therapies for focal MCDs are emerging. Notably, mutations that lead to abnormal a...
Source: Neurotherapeutics - October 4, 2021 Category: Neurology Source Type: research

Axonal Charcot-Marie-Tooth Disease: from Common Pathogenic Mechanisms to Emerging Treatment Opportunities
AbstractInherited peripheral neuropathies are a genetically and phenotypically diverse group of disorders that lead to degeneration of peripheral neurons with resulting sensory and motor dysfunction. Genetic neuropathies that primarily cause axonal degeneration, as opposed to demyelination, are most often classified as Charcot-Marie-Tooth disease type 2 (CMT2) and are the focus of this review. Gene identification efforts over the past three decades have dramatically expanded the genetic landscape of CMT and revealed several common pathological mechanisms among various forms of the disease. In some cases, identification of ...
Source: Neurotherapeutics - October 4, 2021 Category: Neurology Source Type: research

Neuroprotective Roles of the Adenosine A3 Receptor Agonist AST-004 in Mouse Model of Traumatic Brain Injury
AbstractTraumatic brain injury (TBI) remains one of the greatest public health concerns with increasing morbidity and mortality rates worldwide. Our group reported that stimulation of astrocyte mitochondrial metabolism by P2Y1 receptor agonists significantly reduced cerebral edema and reactive gliosis in a TBI model. Subsequent data on the pharmacokinetics (PK) and rapid metabolism of these compounds suggested that neuroprotection was likely mediated by a metabolite, AST-004, which binding data indicated was an adenosine A3 receptor (A3R) agonist. The neuroprotective efficacy of AST-004 was tested in a control closed corti...
Source: Neurotherapeutics - October 4, 2021 Category: Neurology Source Type: research

Precision Therapy for Epilepsy Related to Brain Malformations
AbstractMalformations of cortical development (MCDs) represent a range of neurodevelopmental disorders that are collectively common causes of developmental delay and epilepsy, especially refractory childhood epilepsy. Initial treatment with antiseizure medications is empiric, and consideration of surgery is the standard of care for eligible patients with medically refractory epilepsy. In the past decade, advances in next generation sequencing technologies have accelerated progress in understanding the genetic etiologies of MCDs, and precision therapies for focal MCDs are emerging. Notably, mutations that lead to abnormal a...
Source: Neurotherapeutics - October 4, 2021 Category: Neurology Source Type: research

Axonal Charcot-Marie-Tooth Disease: from Common Pathogenic Mechanisms to Emerging Treatment Opportunities
AbstractInherited peripheral neuropathies are a genetically and phenotypically diverse group of disorders that lead to degeneration of peripheral neurons with resulting sensory and motor dysfunction. Genetic neuropathies that primarily cause axonal degeneration, as opposed to demyelination, are most often classified as Charcot-Marie-Tooth disease type 2 (CMT2) and are the focus of this review. Gene identification efforts over the past three decades have dramatically expanded the genetic landscape of CMT and revealed several common pathological mechanisms among various forms of the disease. In some cases, identification of ...
Source: Neurotherapeutics - October 4, 2021 Category: Neurology Source Type: research

Clinical Trial Design for Disease-Modifying Therapies for Genetic Epilepsies
AbstractAlthough trials with anti-seizure medications (ASMs) have not shown clear anti-epileptogenic or disease-modifying activity in humans to date, rapid advancements in genomic technology and emerging gene-mediated and gene replacement options offer hope for the successful development of disease-modifying therapies (DMTs) for genetic epilepsies. In fact, more than 26 potential DMTs are in various stages of preclinical and/or clinical development for genetic syndromes associated with epilepsy. The scope of disease-modification includes but is not limited to effects on the underlying pathophysiology, the condition ’...
Source: Neurotherapeutics - September 30, 2021 Category: Neurology Source Type: research

Lessons from Injury: How Nerve Injury Studies Reveal Basic Biological Mechanisms and Therapeutic Opportunities for Peripheral Nerve Diseases
AbstractSince Waller and Cajal in the nineteenth and early twentieth centuries, laboratory traumatic peripheral nerve injury studies have provided great insight into cellular and molecular mechanisms governing axon degeneration and the responses of Schwann cells, the major glial cell type of peripheral nerves. It is now evident that pathways underlying injury-induced axon degeneration and the Schwann cell injury-specific state, the repair Schwann cell, are relevant to many inherited and acquired disorders of peripheral nerves. This review provides a timely update on the molecular understanding of axon degeneration and form...
Source: Neurotherapeutics - September 30, 2021 Category: Neurology Source Type: research

Screening Platforms for Genetic Epilepsies —Zebrafish, iPSC-Derived Neurons, and Organoids
AbstractRecent advances in molecular and cellular engineering, such as human cell reprogramming, genome editing, and patient-specific organoids, have provided unprecedented opportunities for investigating human disorders in both animals and human-based models at an improved pace and precision. This progress will inevitably lead to the development of innovative drug-screening platforms and new patient-specific therapeutics. In this review, we discuss recent advances that have been made using zebrafish and human-induced pluripotent stem cell (iPSC) –derived neurons and organoids for modeling genetic epilepsies. We also...
Source: Neurotherapeutics - September 30, 2021 Category: Neurology Source Type: research

Novel Approaches to Prevent Epileptogenesis After Traumatic Brain Injury
AbstractTraumatic brain injury (TBI) is defined as an alteration in brain function or other evidence of brain pathology caused by an external force. When epilepsy develops following TBI, it is known as post-traumatic epilepsy (PTE). PTE occurs in a subset of patients suffering from different types and severities of TBI, occurs more commonly following severe injury, and greatly impacts the quality of life for patients recovering from TBI. Similar to other types of epilepsy, PTE is often refractory to drug treatment with standard anti-seizure drugs. No therapeutic approaches have proven successful in the clinic to prevent th...
Source: Neurotherapeutics - September 30, 2021 Category: Neurology Source Type: research

Clinical Trial Design for Disease-Modifying Therapies for Genetic Epilepsies
AbstractAlthough trials with anti-seizure medications (ASMs) have not shown clear anti-epileptogenic or disease-modifying activity in humans to date, rapid advancements in genomic technology and emerging gene-mediated and gene replacement options offer hope for the successful development of disease-modifying therapies (DMTs) for genetic epilepsies. In fact, more than 26 potential DMTs are in various stages of preclinical and/or clinical development for genetic syndromes associated with epilepsy. The scope of disease-modification includes but is not limited to effects on the underlying pathophysiology, the condition ’...
Source: Neurotherapeutics - September 30, 2021 Category: Neurology Source Type: research

Lessons from Injury: How Nerve Injury Studies Reveal Basic Biological Mechanisms and Therapeutic Opportunities for Peripheral Nerve Diseases
AbstractSince Waller and Cajal in the nineteenth and early twentieth centuries, laboratory traumatic peripheral nerve injury studies have provided great insight into cellular and molecular mechanisms governing axon degeneration and the responses of Schwann cells, the major glial cell type of peripheral nerves. It is now evident that pathways underlying injury-induced axon degeneration and the Schwann cell injury-specific state, the repair Schwann cell, are relevant to many inherited and acquired disorders of peripheral nerves. This review provides a timely update on the molecular understanding of axon degeneration and form...
Source: Neurotherapeutics - September 30, 2021 Category: Neurology Source Type: research

Screening Platforms for Genetic Epilepsies —Zebrafish, iPSC-Derived Neurons, and Organoids
AbstractRecent advances in molecular and cellular engineering, such as human cell reprogramming, genome editing, and patient-specific organoids, have provided unprecedented opportunities for investigating human disorders in both animals and human-based models at an improved pace and precision. This progress will inevitably lead to the development of innovative drug-screening platforms and new patient-specific therapeutics. In this review, we discuss recent advances that have been made using zebrafish and human-induced pluripotent stem cell (iPSC) –derived neurons and organoids for modeling genetic epilepsies. We also...
Source: Neurotherapeutics - September 30, 2021 Category: Neurology Source Type: research

Novel Approaches to Prevent Epileptogenesis After Traumatic Brain Injury
AbstractTraumatic brain injury (TBI) is defined as an alteration in brain function or other evidence of brain pathology caused by an external force. When epilepsy develops following TBI, it is known as post-traumatic epilepsy (PTE). PTE occurs in a subset of patients suffering from different types and severities of TBI, occurs more commonly following severe injury, and greatly impacts the quality of life for patients recovering from TBI. Similar to other types of epilepsy, PTE is often refractory to drug treatment with standard anti-seizure drugs. No therapeutic approaches have proven successful in the clinic to prevent th...
Source: Neurotherapeutics - September 30, 2021 Category: Neurology Source Type: research

Comparative Effectiveness and Tolerability of the Pharmacology of Monoclonal Antibodies Targeting the Calcitonin Gene-Related Peptide and Its Receptor for the Prevention of Chronic Migraine: a Network Meta-analysis of Randomized Controlled Trials
AbstractMonoclonal antibodies (mAbs) acting on the calcitonin gene-related peptide (CGRP) or on its receptor are new therapeutic biologics to prevent chronic migraine (CM). Four mAbs acting on the CGRP or on its receptor are new therapeutic biologics to prevent CM. The aim of current network meta-analysis (NMA) was to compare the efficacy and acceptability of CGRP mAbs with onabotulinumtoxinA or topiramate for CM. We included randomized controlled trials (RCTs) examining CGRP mAbs and onabotulinumtoxinA or topiramate in patients with CM. All network meta-analytic procedures were conducted using the frequentist model. The p...
Source: Neurotherapeutics - September 27, 2021 Category: Neurology Source Type: research

Differential Effects of Fingolimod and Natalizumab on Magnetic Resonance Imaging Measures in Relapsing –Remitting Multiple Sclerosis
AbstractFingolimod and natalizumab are approved disease-modifying drugs in relapsing –remitting multiple sclerosis (RRMS). The two drugs have different modes of action and may therefore influence different aspects of MS-related tissue damage. In this retrospective cohort study, we longitudinally compared patients treated with fingolimod and patients treated with natalizumab by mea sures based on structural magnetic resonance imaging (MRI). We included patients with RRMS given that two standardized MRI scans under the same drug were available with an interval of at least 6 months both from therapy start to baseli...
Source: Neurotherapeutics - September 24, 2021 Category: Neurology Source Type: research

Predictors of Ocrelizumab Effectiveness in Patients with Multiple Sclerosis
SummaryData regarding effectiveness and safety of ocrelizumab in the post-marking setting are lacking. The aim of our study was to provide effectiveness and safety data of ocrelizumab treatment in patients with relapsing –remitting (RR-) and progressive multiple sclerosis (PMS) and to evaluate clinical and immunological predictors of early treatment response. In this single-center prospective observational study, we investigated effectiveness outcomes (time-to-confirmed disability worsening, time-to-first relapse, time-to-first evidence of MRI activity and time-to-first evidence of disease activity), clinical and imm...
Source: Neurotherapeutics - September 22, 2021 Category: Neurology Source Type: research

N-Acylethanolamine Acid Amidase Inhibition Potentiates Morphine Analgesia and Delays the Development of Tolerance
This study aimed to test the hypothesis that NAAA inhibition, with the novel brain permeable NAAA inhibitor AM11095, modulates morphine ’s antinociceptive effects and attenuates the development of morphine tolerance in rats. We tested this hypothesis by measuring the pain threshold to noxious mechanical stimuli and, as a neural correlate, we conducted in vivo electrophysiological recordings from pain-sensitive locus coeruleus (LC) noradrenergic neurons in anesthetized rats. AM11095 dose-dependently (3–30 mg/kg) enhanced the antinociceptive effects of morphine and delayed the development of tolerance to chr...
Source: Neurotherapeutics - September 22, 2021 Category: Neurology Source Type: research

Predictors of Ocrelizumab Effectiveness in Patients with Multiple Sclerosis
SummaryData regarding effectiveness and safety of ocrelizumab in the post-marking setting are lacking. The aim of our study was to provide effectiveness and safety data of ocrelizumab treatment in patients with relapsing –remitting (RR-) and progressive multiple sclerosis (PMS) and to evaluate clinical and immunological predictors of early treatment response. In this single-center prospective observational study, we investigated effectiveness outcomes (time-to-confirmed disability worsening, time-to-first relapse, time-to-first evidence of MRI activity and time-to-first evidence of disease activity), clinical and imm...
Source: Neurotherapeutics - September 22, 2021 Category: Neurology Source Type: research

N-Acylethanolamine Acid Amidase Inhibition Potentiates Morphine Analgesia and Delays the Development of Tolerance
This study aimed to test the hypothesis that NAAA inhibition, with the novel brain permeable NAAA inhibitor AM11095, modulates morphine ’s antinociceptive effects and attenuates the development of morphine tolerance in rats. We tested this hypothesis by measuring the pain threshold to noxious mechanical stimuli and, as a neural correlate, we conducted in vivo electrophysiological recordings from pain-sensitive locus coeruleus (LC) noradrenergic neurons in anesthetized rats. AM11095 dose-dependently (3–30 mg/kg) enhanced the antinociceptive effects of morphine and delayed the development of tolerance to chr...
Source: Neurotherapeutics - September 22, 2021 Category: Neurology Source Type: research

Novel Immunological and Therapeutic Insights in Guillain-Barr é Syndrome and CIDP
SummaryInflammatory neuropathies are a heterogeneous group of rare diseases of the peripheral nervous system that include acute and chronic diseases, such as Guillain-Barr é syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The etiology and pathophysiological mechanisms of inflammatory neuropathies are only partly known, but are considered autoimmune disorders in which an aberrant immune response, including cellular and humoral comp onents, is directed towards components of the peripheral nerve causing demyelination and axonal damage. Therapy of these disorders includes broad-spect...
Source: Neurotherapeutics - September 21, 2021 Category: Neurology Source Type: research

Upregulation of AQP4 Improves Blood –Brain Barrier Integrity and Perihematomal Edema Following Intracerebral Hemorrhage
AbstractIn intracerebral hemorrhage (ICH), delayed secondary neural damages largely occur from perihematomal edema (PHE) resulting from the disruption of the blood –brain barrier (BBB). PHE is often considered the principal cause of morbidity and mortality in patients with ICH. Nevertheless, the main cellular mechanism as well as the specific BBB component involved in the formation of PHE after ICH remains elusive. Herein, we evaluated the role of AQP4, a wa ter channel expressed on the astrocytes of the BBB, in the formation of PHE in ICH. The static and dynamic functions of the BBB were evaluated by analyzing the m...
Source: Neurotherapeutics - September 20, 2021 Category: Neurology Source Type: research

Diagnostic Considerations in the Epilepsies —Testing Strategies, Test Type Advantages, and Limitations
AbstractThe role of genetics in epilepsy has been recognized for a long time. Over the past decade, genome-wide technologies have identified numerous genes and variants associated with epilepsy. In the clinical setting, a myriad of genetic testing options are available, and a subset of specific genetic diagnoses have management implications. Furthermore, genetic testing can be a dynamic process. As a result, fundamental knowledge about genetics and genomics has become essential for all specialists. Here, we review current knowledge of the genetic contribution to various types of epilepsy, provide an overview of types of ge...
Source: Neurotherapeutics - September 16, 2021 Category: Neurology Source Type: research

Emerging Gene and Small Molecule Therapies for the Neurodevelopmental Disorder Angelman Syndrome
AbstractAngelman syndrome (AS) is a rare (~1:15,000) neurodevelopmental disorder characterized by severe developmental delay and intellectual disability, impaired communication skills, and a high prevalence of seizures, sleep disturbances, ataxia, motor deficits, and microcephaly. AS is caused by loss-of-function of the maternally inheritedUBE3A gene.UBE3A is located on chromosome 15q11 –13 and is biallelically expressed throughout the body but only maternally expressed in the brain due to an RNA antisense transcript that silences the paternal copy. There is currently no cure for AS, but advancements in small molecul...
Source: Neurotherapeutics - September 15, 2021 Category: Neurology Source Type: research

ASENT2021 Annual Meeting Abstracts
(Source: Neurotherapeutics)
Source: Neurotherapeutics - September 15, 2021 Category: Neurology Source Type: research

Heat Shock Protein 70 as a Sex-Skewed Regulator of α-Synucleinopathy
AbstractThe role of molecular chaperones, such as heat shock protein 70 (Hsp70), is not typically studied as a function of biological sex, but by addressing this gap we might improve our understanding of proteinopathic disorders that predominate in one sex. Therefore, we exposed male or female primary hippocampal cultures to preformed α-synuclein fibrils in a model of early-stage Lewy pathology. We first discovered that two mechanistically distinct inhibitors of Hsp70 function increased phospho-α-synuclein+ inclusions more robustly in male-derived neurons. Because Hsp70 is released into extracellular compartmen...
Source: Neurotherapeutics - September 15, 2021 Category: Neurology Source Type: research

Emerging Gene and Small Molecule Therapies for the Neurodevelopmental Disorder Angelman Syndrome
AbstractAngelman syndrome (AS) is a rare (~1:15,000) neurodevelopmental disorder characterized by severe developmental delay and intellectual disability, impaired communication skills, and a high prevalence of seizures, sleep disturbances, ataxia, motor deficits, and microcephaly. AS is caused by loss-of-function of the maternally inheritedUBE3A gene.UBE3A is located on chromosome 15q11 –13 and is biallelically expressed throughout the body but only maternally expressed in the brain due to an RNA antisense transcript that silences the paternal copy. There is currently no cure for AS, but advancements in small molecul...
Source: Neurotherapeutics - September 15, 2021 Category: Neurology Source Type: research

ASENT2021 Annual Meeting Abstracts
(Source: Neurotherapeutics)
Source: Neurotherapeutics - September 15, 2021 Category: Neurology Source Type: research

Heat Shock Protein 70 as a Sex-Skewed Regulator of α-Synucleinopathy
AbstractThe role of molecular chaperones, such as heat shock protein 70 (Hsp70), is not typically studied as a function of biological sex, but by addressing this gap we might improve our understanding of proteinopathic disorders that predominate in one sex. Therefore, we exposed male or female primary hippocampal cultures to preformed α-synuclein fibrils in a model of early-stage Lewy pathology. We first discovered that two mechanistically distinct inhibitors of Hsp70 function increased phospho-α-synuclein+ inclusions more robustly in male-derived neurons. Because Hsp70 is released into extracellular compartmen...
Source: Neurotherapeutics - September 15, 2021 Category: Neurology Source Type: research

Characterization of Selenium Compounds for Anti-ferroptotic Activity in Neuronal Cells and After Cerebral Ischemia –Reperfusion Injury
AbstractThe emergence of ferroptosis as a cell death pathway associated with brain disorders including stroke and neurodegenerative diseases emphasizes the need to develop therapeutics able to target the brain and to protect neurons from ferroptotic death. Selenium plays an essential role in reducing lipid peroxidation generated during ferroptosis through its incorporation into the catalytic site of glutathione peroxidase 4. Here, we compared the anti-ferroptotic activity of several organic and inorganic selenium compounds: methylselenocysteine, selenocystine, selenomethionine, selenocystamine, ebselen, sodium selenite, an...
Source: Neurotherapeutics - September 8, 2021 Category: Neurology Source Type: research

Disease Reactivation after Fingolimod Discontinuation in Pregnant Multiple Sclerosis Patients
AbstractRecent studies estimated an incidence of 4 –25% of disease rebound after withdrawal of fingolimod (FTY) for any reason, but specific data on disease reactivation after FTY withdrawal due to pregnancy are limited. The aim of the study was to evaluate the frequency and predictors of disease reactivation in patients who stopped FTY for pregna ncy. A multicentre retrospective cohort study was conducted in four Italian MS centres in 2013–2019. Both planned and unplanned pregnancies were included. The annualized relapse rate (ARR) was calculated before FTY treatment, during FTY treatment, during pregnancy and...
Source: Neurotherapeutics - September 7, 2021 Category: Neurology Source Type: research

Hybrid Nanoparticles as a Novel Tool for Regulating Psychosine-Induced Neuroinflammation and Demyelination In Vitro and Ex vivo
We present evidence that lecithin/chitosan nanoparticles prevent damage ass ociated with psychosine by sequestering the neurotoxic sphingolipid via physicochemical hydrophobic interactions. We showed how nanoparticles prevented the cytotoxicity caused by psychosine in cultured human astrocytes in vitro, and how the nanoparticle size and PDI augmented while the electrostatic charges of the surface decreased, suggesting a direct interaction between psychosine and the nanoparticles. Moreover, we studied the effects of nanoparticles ex vivo using mouse cerebellar organotypic cultures, observing that nanoparticles prevented the...
Source: Neurotherapeutics - September 3, 2021 Category: Neurology Source Type: research

The Link Between Alzheimer Disease and Herpes Simplex Virus Infection: Better Late Than Never, or Better Never Than Late?
(Source: Neurotherapeutics)
Source: Neurotherapeutics - September 3, 2021 Category: Neurology Source Type: research

Multiple Sclerosis: Switching from Natalizumab to Other High-Efficacy Treatments to Mitigate Progressive Multifocal Leukoencephalopathy Risk
(Source: Neurotherapeutics)
Source: Neurotherapeutics - September 3, 2021 Category: Neurology Source Type: research

Hybrid Nanoparticles as a Novel Tool for Regulating Psychosine-Induced Neuroinflammation and Demyelination In Vitro and Ex vivo
We present evidence that lecithin/chitosan nanoparticles prevent damage ass ociated with psychosine by sequestering the neurotoxic sphingolipid via physicochemical hydrophobic interactions. We showed how nanoparticles prevented the cytotoxicity caused by psychosine in cultured human astrocytes in vitro, and how the nanoparticle size and PDI augmented while the electrostatic charges of the surface decreased, suggesting a direct interaction between psychosine and the nanoparticles. Moreover, we studied the effects of nanoparticles ex vivo using mouse cerebellar organotypic cultures, observing that nanoparticles prevented the...
Source: Neurotherapeutics - September 3, 2021 Category: Neurology Source Type: research