Insights into the mechanisms of epilepsy from structural biology of LGI1-ADAM22.

Insights into the mechanisms of epilepsy from structural biology of LGI1-ADAM22. Cell Mol Life Sci. 2019 Aug 20;: Authors: Yamagata A, Fukai S Abstract Epilepsy is one of the most common brain disorders, which can be caused by abnormal synaptic transmissions. Many epilepsy-related mutations have been identified in synaptic ion channels, which are main targets for current antiepileptic drugs. One of the novel potential targets for therapy of epilepsy is a class of non-ion channel-type epilepsy-related proteins. The leucine-rich repeat glioma-inactivated protein 1 (LGI1) is a neuronal secreted protein, and has been extensively studied as a product of a causative gene for autosomal dominant lateral temporal lobe epilepsy (ADLTE; also known as autosomal dominant partial epilepsy with auditory features [ADPEAF]). At least 43 mutations of LGI1 have been found in ADLTE families. Additionally, autoantibodies against LGI1 in limbic encephalitis are associated with amnesia, seizures, and cognitive dysfunction. Although the relationship of LGI1 with synaptic transmission and synaptic disorders has been studied genetically, biochemically, and clinically, the structural mechanism of LGI1 remained largely unknown until recently. In this review, we introduce insights into pathogenic mechanisms of LGI1 from recent structural studies on LGI1 and its receptor, ADAM22. We also discuss the mechanism for pathogenesis of autoantibodies against LGI1, and the potential of chemi...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research

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Publication date: Available online 15 January 2020Source: Ticks and Tick-borne DiseasesAuthor(s): Dana Zubriková, Maria Wittmann, Václav Hönig, Pavel Švec, Bronislava Víchová, Sandra Essbauer, Gerhard Dobler, Libor Grubhoffer, Kurt PfisterAbstractLyme borreliosis and tick-borne encephalitis (TBE) are the most common tick-borne diseases in Germany. We collected Ixodes ricinus ticks from 16 high-risk and four low-risk sites distributed in Lower Bavaria and Upper Palatinate based on the number of human TBE cases recorded at the Robert Koch Institute from 2001 to 2009. A total of 8805 qu...
Source: Ticks and Tick borne Diseases - Category: Zoology Source Type: research
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Source: Health, Risk and Society - Category: International Medicine & Public Health Authors: Source Type: research
thier Caterina Merla Mariateresa Mancuso Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Despite the progress of new treatments, the risk of recurrence, morbidity, and death remains significant and the long-term adverse effects in survivors are substantial. The fraction of cancer stem-like cells (CSCs) because of their self-renewal ability and multi-lineage differentiation potential is critical for tumor initiation, growth, and resistance to therapies. For the development of new CSC-targeted therapies, further in-depth studies are needed using enriched and stable MB-CSCs populations. This w...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Authors: Amin U, Benbadis SR Abstract Introduction: Despite the advances in the diagnosis and treatment of epilepsy, approximately 30% of the patients remain intractable. Uncontrolled seizures have deleterious consequences, including brain damage, cognitive decline, decreased quality of life, and increased mortality.Areas covered: In this article, the authors discuss the treatment gap in patients with intractable epilepsy and the possible mechanisms of drug resistance. The authors provide a treatment algorithm for patients with intractable epilepsy, including non-pharmacological treatment options, such as diet, neuros...
Source: Expert Review of Neurotherapeutics - Category: Neurology Tags: Expert Rev Neurother Source Type: research
Authors: Wang X, Zhao J Abstract Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder causing progressive memory loss and cognitive impairment. The aberrant accumulation of amyloid‑β (Aβ) and neuroinflammation are two major events in AD. Aβ‑induced neurotoxicity and oxidative stress are also involved in the pathogenesis of AD. The purpose of the current study was to investigate the effect of compound porcine cerebroside and ganglioside injection (CPCGI) on the progression of AD, and to explore the molecular mechanism. In vivo and in vitro models of AD were established...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
Niels Hansen1,2* 1Department of Epileptology, University of Bonn Medical Center, Bonn, Germany2Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany Limbic encephalitis (LE) is an autoimmune disease defined by clinical criteria, such as seizures, psychiatric and in particular working memory abnormalities in conjunction with apparative criteria underlying structural or functional changes in the temporal lobe according to autoimmune encephalitis guidelines (1). Working memory encompasses a transient encoding of information in readiness for further processing within a time windo...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Limbic encephalitis (LE) is an inflammatory brain disorder that predominantly involves the gray matter of the medial temporal lobes, resulting in mood and behavioral changes, seizures, and difficulty in forming new memories, often with retrograde memory loss.1 In most patients, the presence of an inflammatory process in the medial temporal lobes and hippocampi is visible on MRI fluid-attenuated inversion recovery (FLAIR) sequences and supported by demonstration of pleocytosis in the CSF.2–4 Nevertheless, several infections, systemic inflammatory diseases, and autoimmune mechanisms may lead to this syndrome (table). T...
Source: Neurology - Category: Neurology Authors: Tags: Autoimmune diseases, Encephalitis, Memory EDITORIALS Source Type: research
Conclusions: Anti-LGI1 encephalitis is a homogenous clinical syndrome, showing early FBDS and other focal seizures with subtle clinical manifestations, followed by memory disturbances. Better recognition will lead to earlier diagnosis, essential for prompt start of treatment. Long-term outcome of surviving patients is mostly favorable, but relapses are common.
Source: Neurology - Category: Neurology Authors: Tags: Autoimmune diseases, Encephalitis, All Epilepsy/Seizures ARTICLE Source Type: research
Conclusions: FBDS, which affects the ipsilateral face and arm, is a disorder in the watershed between epilepsy and movement disorders, and a transitional presentation of limbic encephalitis. While FBDS is refractory to antiepileptics, the response to immunotherapy can be robust.1, 2 This case illustrates that slow saccades may be an additional early symptom along the spectrum among faciobrachial dystonic seizures and limbic encephalitis. Typically, episodes have no ictal EEG correlate. Irani and colleagues found only 7/29 patients with FBDS had EEG positive episodes.1 MRI findings may be normal or include increased signal ...
Source: Neurology - Category: Neurology Authors: Tags: Movement Disorders ePoster Session Source Type: research
Encephalitis associated with antibodies against leucine-rich glioma-inactivated 1 (LGI1) protein is increasingly recognized as an auto-immune disorder associated with characteristic tonic-dystonic seizures. The cortical or subcortical origin of these motor events is not clear. Some patients also present with different epileptic seizures and with cognitive impairment. The frequency of these features and their timing during the natural history of this encephalitis have not been fully described. We therefore reviewed data from 34 patients harbouring antibodies against LGI1 protein (21–81 years, median age 64) referred t...
Source: Brain - Category: Neurology Authors: Tags: Epilepsy and Sleep Original Articles Source Type: research
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