33,605 results match your criteria Lead Encephalopathy


Inhibition of Death-associated Protein Kinase 1 Attenuates Cis P-tau and Neurodegeneration in Traumatic Brain Injury.

Prog Neurobiol 2021 May 9:102072. Epub 2021 May 9.

Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA; Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA. Electronic address:

Traumatic brain injury (TBI) is the leading cause of mortality and disability in young people and may lead to the development of progressive neurodegeneration, such as that observed in chronic traumatic encephalopathy. We have recently found that the conformation-specific cis phosphorylated form of tau (cis P-tau) is a major early driver of neurodegeneration after TBI. However, not much is known about how cis P-tau is regulated in TBI. Read More

View Article and Full-Text PDF

Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer's Disease.

Neuropsychiatr Dis Treat 2021 4;17:1311-1339. Epub 2021 May 4.

Department of Pathophysiology, Medical University of Gdansk, Gdansk, Poland.

Alzheimer's disease (AD) is the most common form of dementia and aging is the most common risk factor for developing the disease. The etiology of AD is not known but AD may be considered as a clinical syndrome with multiple causal pathways contributing to it. The amyloid cascade hypothesis, claiming that excess production or reduced clearance of amyloid-beta (Aβ) and its aggregation into amyloid plaques, was accepted for a long time as the main cause of AD. Read More

View Article and Full-Text PDF

Targeting Poison Exons to Treat Developmental and Epileptic Encephalopathy.

Dev Neurosci 2021 May 10:1-6. Epub 2021 May 10.

Ken and Ruth Davee Department of Neurology, Northwestern University School of Medicine, Chicago, Illinois, USA.

Developmental and epileptic encephalopathies (DEEs) describe a subset of neurodevelopmental disorders categorized by refractory epilepsy that is often associated with intellectual disability and autism spectrum disorder. The majority of DEEs are now known to have a genetic basis with de novo coding variants accounting for the majority of cases. More recently, a small number of individuals have been identified with intronic SCN1A variants that result in alternative splicing events that lead to ectopic inclusion of poison exons (PEs). Read More

View Article and Full-Text PDF

Mutation-Related Disorders: Clinical and Genetic Features.

Front Pediatr 2021 21;9:657256. Epub 2021 Apr 21.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

encodes an α1 isoform of Na/K-ATPase, which is expressed abundantly in kidneys and central nervous system. variants may cause Na/K-ATPase loss of function and lead to a wide spectrum of phenotypes. This study aims to summarize the clinical and genetic features of mutation-related disorders and explore the potential correlations between phenotypes and genotypes. Read More

View Article and Full-Text PDF

Cholestasis and behavioral disorders.

Gastroenterol Hepatol Bed Bench 2021 ;14(2):95-107

Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran.

Acute and chronic failure in liver function may give rise to cognitive and non-cognitive impairments in the brain, namely hepatic encephalopathy (HE). Liver diseases may cause cholestasis, which is defined as the impaired secretion of bile. It is characterized by the accumulation of substances in plasma that are normally excreted in bile such as bile acids. Read More

View Article and Full-Text PDF
January 2021

Canavan Disease as a Model for Gene Therapy-Mediated Myelin Repair.

Front Cell Neurosci 2021 23;15:661928. Epub 2021 Apr 23.

Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, United States.

In recent years, the scientific and therapeutic fields for rare, genetic central nervous system (CNS) diseases such as leukodystrophies, or white matter disorders, have expanded significantly in part due to technological advancements in cellular and clinical screenings as well as remedial therapies using novel techniques such as gene therapy. However, treatments aimed at normalizing the pathological changes associated with leukodystrophies have especially been complicated due to the innate and variable effects of glial abnormalities, which can cause large-scale functional deficits in developmental myelination and thus lead to downstream neuronal impairment. Emerging research in the past two decades have depicted glial cells, particularly oligodendrocytes and astrocytes, as key, regulatory modulators in constructing and maintaining myelin function and neuronal viability. Read More

View Article and Full-Text PDF

Gut microbiota modulates the inflammatory response and cognitive impairment induced by sleep deprivation.

Mol Psychiatry 2021 May 7. Epub 2021 May 7.

National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, China.

Sleep deprivation (SD) is increasingly common in modern society, which can lead to the dysregulation of inflammatory responses and cognitive impairment, but the mechanisms remain unclear. Emerging evidence suggests that gut microbiota plays a critical role in the pathogenesis and development of inflammatory and psychiatric diseases, possibly via gut microbiota-brain interactions and neuroinflammation. The present study investigated the impact of SD on gut microbiota composition and explored whether alterations of the gut microbiota play a causal role in chronic inflammatory states and cognitive impairment that are induced by SD. Read More

View Article and Full-Text PDF

Repetitive mild head trauma induces activity mediated lifelong brain deficits in a novel Drosophila model.

Sci Rep 2021 May 6;11(1):9738. Epub 2021 May 6.

Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, 30322, USA.

Mild head trauma, including concussion, can lead to chronic brain dysfunction and degeneration but the underlying mechanisms remain poorly understood. Here, we developed a novel head impact system to investigate the long-term effects of mild head trauma on brain structure and function, as well as the underlying mechanisms in Drosophila melanogaster. We find that Drosophila subjected to repetitive head impacts develop long-term deficits, including impaired startle-induced climbing, progressive brain degeneration, and shortened lifespan, all of which are substantially exacerbated in female flies. Read More

View Article and Full-Text PDF

Discovery of Natural Products Targeting NQO1 via an Approach Combining Network-Based Inference and Identification of Privileged Substructures.

J Chem Inf Model 2021 May 6. Epub 2021 May 6.

Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.

NAD(P)H:quinone oxidoreductase 1 (NQO1) has been shown to be a potential therapeutic target for various human diseases, such as cancer and neurodegenerative disorders. Recent advances in computational methods, especially network-based methods, have made it possible to identify novel compounds for a target with high efficiency and low cost. In this study, we designed a workflow combining network-based methods and identification of privileged substructures to discover new compounds targeting NQO1 from a natural product library. Read More

View Article and Full-Text PDF

Multitarget neuroprotection by Quercetin: changes in gene expression in two perinatal asphyxia models".

Neurochem Int 2021 May 2:105064. Epub 2021 May 2.

Sección Genética Evolutiva, Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay. Electronic address:

Hypoxic-ischemic encephalopathy (HIE) causes mortality and long-term neurologic morbidities in newborns, affecting pathways related to energy failure, excitotoxicity and oxidative stress that often lead to cell death. The whole process of HIE injury is coupled to changes in the expression of a great array of proteins. A nanoliposomal preparation of the flavonoid quercetin has been shown to exert neuroprotective effects in perinatal asphyxia models. Read More

View Article and Full-Text PDF

Obesity-associated hyperleptinemia alters the gliovascular interface of the hypothalamus to promote hypertension.

Cell Metab 2021 Apr 30. Epub 2021 Apr 30.

Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany; Medizinische Klinik and Poliklinik IV, Klinikum der Universität, Ludwig-Maximilians-Universität München, Munich, Germany. Electronic address:

Pathologies of the micro- and macrovascular systems are a hallmark of the metabolic syndrome, which can lead to chronically elevated blood pressure. However, the underlying pathomechanisms involved still need to be clarified. Here, we report that an obesity-associated increase in serum leptin triggers the select expansion of the micro-angioarchitecture in pre-autonomic brain centers that regulate hemodynamic homeostasis. Read More

View Article and Full-Text PDF

Genipin Attenuates Tau Phosphorylation and Aβ Levels in Cellular Models of Alzheimer's Disease.

Mol Neurobiol 2021 May 4. Epub 2021 May 4.

Shenzhen Key Laboratory of Marine Bioresources and Ecology, Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, 518060, People's Republic of China.

Alzheimer's disease (AD) is a devastating brain disorder characterized by neurofibrillary tangles and amyloid plaques. Inhibiting Tau protein and amyloid-beta (Aβ) production or removing these molecules is considered potential therapeutic strategies for AD. Genipin is an aglycone and is isolated from the extract of Gardenia jasminoides Ellis fruit. Read More

View Article and Full-Text PDF

Wernicke Encephalopathy in an Elderly Patient Due to Chronic Malnutrition From an Atypical Diet.

Cureus 2021 Mar 31;13(3):e14210. Epub 2021 Mar 31.

Psychiatry, Lewis Gale Medical Center, Salem, USA.

Wernicke encephalopathy has traditionally been associated with chronic alcohol abuse leading to thiamine deficiency. Clinical symptoms include mentation change, gait ataxia, and oculomotor abnormalities. However, it is often an underdiagnosed condition in patients suffering from chronic malnutrition, especially in the West. Read More

View Article and Full-Text PDF

Genome-wide histone acetylation analysis reveals altered transcriptional regulation in the Parkinson's disease brain.

Mol Neurodegener 2021 05 5;16(1):31. Epub 2021 May 5.

Neuro-SysMed Center of Excellence for Clinical Research in Neurological Diseases, Department of Neurology, Haukeland University Hospital, 5021, Bergen, Norway.

Background: Parkinson's disease (PD) is a complex, age-related neurodegenerative disorder of largely unknown etiology. PD is strongly associated with mitochondrial respiratory dysfunction, which can lead to epigenetic dysregulation and specifically altered histone acetylation. Nevertheless, and despite the emerging role of epigenetics in age-related brain disorders, the question of whether aberrant histone acetylation is involved in PD remains unresolved. Read More

View Article and Full-Text PDF

Brain organoids: a promising model to assess oxidative stress-induced Central Nervous System damage.

Dev Neurobiol 2021 May 3. Epub 2021 May 3.

Department of Biomedical Engineering Sciences, School of Medicine, Loma Linda University, Loma Linda, CA, USA.

Oxidative stress (OS) is one of the most significant propagators of systemic damage with implications for widespread pathologies such as vascular disease, accelerated aging, degenerative disease, inflammation, and traumatic injury. OS can be induced by numerous factors such as environmental conditions, lifestyle choices, disease states, and genetic susceptibility. It is tied to the accumulation of free radicals, mitochondrial dysfunction, and insufficient antioxidant protection, which leads to cell aging and tissue degeneration over time. Read More

View Article and Full-Text PDF

Post hoc assessment of relationship between coronary stenosis, ECG and ventricular function in patients with heart disease.

Can J Physiol Pharmacol 2021 May 3. Epub 2021 May 3.

USF Health Morsani College of Medicine, 33697, Tampa, Florida, United States;

Cardiovascular diseases including cardiac arrhythmias lead to fatal events in patients with coronary artery disease, however clinical associations from echocardiography, electrocardiography (ECG) and biomarkers remain unknown. We sought to identify the factors that may be related to elevated QRS intervals in patients with risk for coronary artery disease. In this study, we performed analysis of clinical data from 503 patients and divided into two groups, i. Read More

View Article and Full-Text PDF

: An Unexpected Cause of Polyarthritis and Meningitis.

J Investig Med High Impact Case Rep 2021 Jan-Dec;9:23247096211012194

University of Florida College of Medicine, Jacksonville, FL, USA.

, a gram-negative coccus, is a major cause of morbidity among sexually active individuals. Hematogenous spread of from the initial site of infection is thought to occur in only 0.5% to 3% of infected patients. Read More

View Article and Full-Text PDF

Feature of cognitive dysfunction in patients with temporal lobe epilepsy and its clinical influencing factors.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Mar;46(3):240-248

Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.

Objectives: To comprehensively analyze the characteristics of cognitive impairment of temporal lobe epilepsy (TLE), and to explore the effects of different lateral patients' cognitive impairment and different clinical factors on cognitive impairment of TLE.

Methods: A total of 84 patients, who met the diagnostic criteria for TLE in the Department of Neurology, Xiangya Hospital, were collected as a patient group, with 36 cases of left TLE and 48 cases of right TLE. A total of 79 healthy volunteers with matching gender, age and education level were selected as a control group. Read More

View Article and Full-Text PDF

Anxiety and depression severity in neuropsychiatric SLE are associated with perfusion and functional connectivity changes of the frontolimbic neural circuit: a resting-state f(unctional) MRI study.

Lupus Sci Med 2021 04;8(1)

Computational Bio-Medicine Laboratory, Institute of Computer Science, Foundation for Research and Technology - Hellas, Heraklion, Crete, Greece

Objective: To examine the hypothesis that perfusion and functional connectivity disturbances in brain areas implicated in emotional processing are linked to emotion-related symptoms in neuropsychiatric SLE (NPSLE).

Methods: Resting-state fMRI (rs-fMRI) was performed and anxiety and/or depression symptoms were assessed in 32 patients with NPSLE and 18 healthy controls (HC). Whole-brain time-shift analysis (TSA) maps, voxel-wise global connectivity (assessed through intrinsic connectivity contrast (ICC)) and within-network connectivity were estimated and submitted to one-sample t-tests. Read More

View Article and Full-Text PDF

Small-Molecule Inhibitors of the RNA M6A Demethylases FTO Potently Support the Survival of Dopamine Neurons.

Int J Mol Sci 2021 Apr 26;22(9). Epub 2021 Apr 26.

Institute of Chemistry, University of Tartu, Ravila 14a, 50411 Tartu, Estonia.

The fat mass and obesity-associated protein (FTO), an RNA N-methyladenosine (mA) demethylase, is an important regulator of central nervous system development, neuronal signaling and disease. We present here the target-tailored development and biological characterization of small-molecule inhibitors of FTO. The active compounds were identified using high-throughput molecular docking and molecular dynamics screening of the ZINC compound library. Read More

View Article and Full-Text PDF

Aberrant Complement System Activation in Neurological Disorders.

Int J Mol Sci 2021 Apr 28;22(9). Epub 2021 Apr 28.

Mossakowski Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, 5 Pawinskiego Street, 02-106 Warsaw, Poland.

The complement system is an assembly of proteins that collectively participate in the functions of the healthy and diseased brain. The complement system plays an important role in the maintenance of uninjured (healthy) brain homeostasis, contributing to the clearance of invading pathogens and apoptotic cells, and limiting the inflammatory immune response. However, overactivation or underregulation of the entire complement cascade within the brain may lead to neuronal damage and disturbances in brain function. Read More

View Article and Full-Text PDF

A Comprehensive Analysis into the Therapeutic Application of Natural Products as SIRT6 Modulators in Alzheimer's Disease, Aging, Cancer, Inflammation, and Diabetes.

Int J Mol Sci 2021 Apr 17;22(8). Epub 2021 Apr 17.

Department of Pharmacy, Brac University, Dhaka 1212, Bangladesh.

Natural products have long been used as drugs to treat a wide array of human diseases. The lead compounds discovered from natural sources are used as novel templates for developing more potent and safer drugs. Natural products produce biological activity by binding with biological macromolecules, since natural products complement the protein-binding sites and natural product-protein interactions are already optimized in nature. Read More

View Article and Full-Text PDF

Key Disease Mechanisms Linked to Alzheimer's Disease in the Entorhinal Cortex.

Int J Mol Sci 2021 Apr 10;22(8). Epub 2021 Apr 10.

Center for Neurodegenerative Diseases and Therapeutics, Discipline of Cellular and Molecular Pharmacology, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.

Alzheimer's disease (AD) is a chronic, neurodegenerative brain disorder affecting millions of Americans that is expected to increase in incidence with the expanding aging population. Symptomatic AD patients show cognitive decline and often develop neuropsychiatric symptoms due to the accumulation of insoluble proteins that produce plaques and tangles seen in the brain at autopsy. Unexpectedly, some clinically normal individuals also show AD pathology in the brain at autopsy (asymptomatic AD, AsymAD). Read More

View Article and Full-Text PDF

Oligodendrocyte Development and Regenerative Therapeutics in Multiple Sclerosis.

Life (Basel) 2021 Apr 9;11(4). Epub 2021 Apr 9.

Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, AP-HP, Hôpital de la Pitié Salpêtrière, Sorbonne Université, 75013 Paris, France.

Myelination by oligodendrocytes (OLs) is an important biological process essential for central nervous system (CNS) development and functions. Oligodendroglial lineage cells undergo several morphological and molecular changes at different stages of their lineage progression into myelinating OLs. The transition steps of the oligodendrocyte progenitor cells (OPCs) to myelinating oligodendrocytes are defined by a specific pattern of regulated gene expression, which is under the control of coordinated signaling pathways. Read More

View Article and Full-Text PDF

The Links between ALS and NF-κB.

Int J Mol Sci 2021 Apr 8;22(8). Epub 2021 Apr 8.

Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, 1015 Lausanne, Switzerland.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease wherein motor neuron degeneration leads to muscle weakness, progressive paralysis, and death within 3-5 years of diagnosis. Currently, the cause of ALS is unknown but, as with several neurodegenerative diseases, the potential role of neuroinflammation has become an increasingly popular hypothesis in ALS research. Indeed, upregulation of neuroinflammatory factors have been observed in both ALS patients and animal models. Read More

View Article and Full-Text PDF

Current Management and Therapeutic Strategies for Cerebral Amyloid Angiopathy.

Int J Mol Sci 2021 Apr 8;22(8). Epub 2021 Apr 8.

Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.

Cerebral amyloid angiopathy (CAA) is characterized by accumulation of amyloid β (Aβ) in walls of leptomeningeal vessels and cortical capillaries in the brain. The loss of integrity of these vessels caused by cerebrovascular Aβ deposits results in fragile vessels and lobar intracerebral hemorrhages. CAA also manifests with progressive cognitive impairment or transient focal neurological symptoms. Read More

View Article and Full-Text PDF

MGMT-Methylation in Non-Neoplastic Diseases of the Central Nervous System.

Int J Mol Sci 2021 Apr 8;22(8). Epub 2021 Apr 8.

Institute of Neuropathology, University Hospital Essen, D-45147 Essen, Germany.

Quantifying O-methylguanine-DNA methyltransferase (MGMT) promoter methylation plays an essential role in assessing the potential efficacy of alkylating agents in the chemotherapy of malignant gliomas. MGMT promoter methylation is considered to be a characteristic of subgroups of certain malignancies but has also been described in various peripheral inflammatory diseases. However, MGMT promoter methylation levels have not yet been investigated in non-neoplastic brain diseases. Read More

View Article and Full-Text PDF

Discovery of a Novel Acetylcholinesterase Inhibitor by Fragment-Based Design and Virtual Screening.

Molecules 2021 Apr 3;26(7). Epub 2021 Apr 3.

Department of Chemistry, Faculty of Pharmacy, Medical University of Sofia, Sofia 1000, Bulgaria.

Despite extensive and intensive research efforts in recent decades, there is still no effective treatment for neurodegenerative diseases. On this background, the use of drugs inhibiting the enzyme acetylcholinesterase (AChE) remains an eternal evergreen in the symptomatic treatment of mild to moderate cognitive impairments. Even more, the cholinergic hypothesis, somewhat forgotten in recent years due to the shift in focus on amyloid cascade, is back to life, and the search for new, more effective AChE inhibitors continues. Read More

View Article and Full-Text PDF

Prospects of Therapeutic Target and Directions for Ischemic Stroke.

Pharmaceuticals (Basel) 2021 Apr 1;14(4). Epub 2021 Apr 1.

Research Institute, e-biogen Inc., Seoul 07282, Korea.

Stroke is a serious, adverse neurological event and the third leading cause of death and disability worldwide. Most strokes are caused by a block in cerebral blood flow, resulting in neurological deficits through the death of brain tissue. Recombinant tissue plasminogen activator (rt-PA) is currently the only immediate treatment medication for stroke. Read More

View Article and Full-Text PDF

Celia's Encephalopathy (-Gene-Related): Current Understanding.

J Clin Med 2021 Apr 1;10(7). Epub 2021 Apr 1.

UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS-CIMUS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.

Seipin, encoded by the gene, is a protein that in humans is expressed mainly in the central nervous system. Uniquely, certain variants in can cause both generalized congenital lipodystrophy type 2, upper and/or lower motor neuron diseases, or progressive encephalopathy, with a poor prognosis during childhood. The latter, Celia's encephalopathy, which may or may not be associated with generalized lipodystrophy, is caused by the c. Read More

View Article and Full-Text PDF