Beta Amyloid Peptide: Research Paper : Human Herpesviruses 6A and 6B in Brain Diseases: Association versus Causation

Human Herpesviruses 6A and 6B in Brain Diseases: Association versus Causation

Abstract

SUMMARYHuman herpesvirus 6A (HHV-6A) and human herpesvirus 6B (HHV-6B), collectively termed HHV-6A/B, are neurotropic viruses that permanently infect most humans from an early age. Although most people infected with these viruses appear to suffer no ill effects, the viruses are a well-established cause of encephalitis in immunocompromised patients. In this review, we summarize the evidence that the viruses may also be one trigger for febrile seizures (including febrile status epilepticus) in immunocompetent infants and children, mesial temporal lobe epilepsy, multiple sclerosis (MS), and, possibly, Alzheimer's disease. We propose criteria for linking ubiquitous infectious agents capable of producing lifelong infection to any neurologic disease, and then we examine to what extent these criteria have been met for these viruses and these diseases.

Keywords: Alzheimer's disease; febrile seizures; febrile status epilepticus; human herpesvirus 6A; human herpesvirus 6B; mesial temporal lobe epilepsy; multiple sclerosis.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33177186/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Investigational Assay for Haplotype Phasing of the Huntingtin Gene

Investigational Assay for Haplotype Phasing of the Huntingtin Gene

Abstract

Novel treatments for Huntington's disease (HD), a progressive neurodegenerative disorder, include selective targeting of the mutant allele of the huntingtin gene (mHTT) carrying the abnormally expanded disease-causing cytosine-adenine-guanine (CAG) repeat. WVE-120101 and WVE-120102 are investigational stereopure antisense oligonucleotides that enable selective suppression of mHTT by targeting single-nucleotide polymorphisms (SNPs) that are in haplotype phase with the CAG repeat expansion. Recently developed long-read sequencing technologies can capture CAG expansions and distant SNPs of interest and potentially facilitate haplotype-based identification of patients for clinical trials of oligonucleotide therapies. However, improved methods are needed to phase SNPs with CAG repeat expansions directly and reliably without need for familial genotype/haplotype data. Our haplotype phasing method uses single-molecule real-time sequencing and a custom algorithm to determine with confidence bases at SNPs on mutant alleles, even without familial data. Herein, we summarize this methodology and validate the approach using patient-derived samples with known phasing results. Comparison of experimentally measured CAG repeat lengths, heterozygosity, and phasing with previously determined results showed improved performance. Our methodology enables the haplotype phasing of SNPs of interest and the disease-causing, expanded CAG repeat of the huntingtin gene, enabling accurate identification of patients with HD eligible for allele-selective clinical studies.

Keywords: Huntington's disease; antisense oligonucleotide; long-read sequencing; mRNA; single-nucleotide polymorphism.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33209959/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Strictly Lobar Microbleeds Reflect Amyloid Angiopathy Regardless of Cerebral and Cerebellar Compartments

Strictly Lobar Microbleeds Reflect Amyloid Angiopathy Regardless of Cerebral and Cerebellar Compartments

Abstract

Background and purpose: We aimed to determine whether lobar cerebellar microbleeds or concomitant lobar cerebellar and deep microbleeds, in the presence of lobar cerebral microbleeds, attribute to underlying advanced cerebral amyloid angiopathy pathology or hypertensive arteriopathy.

Methods: We categorized 71 patients with suspected cerebral amyloid angiopathy markers (regardless of the presence of deep and cerebellar microbleeds) into 4 groups according to microbleed distribution: L (strictly lobar cerebral, n=33), L/LCbll (strictly lobar cerebral and strictly lobar cerebellar microbleeds, n=13), L/Cbll/D (lobar, cerebellar, and deep microbleeds, n=17), and L/D (lobar and deep, n=8). We additionally categorized patients with cerebellar microbleeds into 2 groups according to dentate nucleus involvement: strictly lobar cerebellar (n=16) and dentate (n=14). We then compared clinical characteristics, Aβ (amyloid-β) positivity on PET (positron emission tomography), magnetic resonance imaging cerebral amyloid angiopathy markers, and cerebral small vessel disease burden among groups.

Results: The frequency of Aβ positivity was higher in the L and L/LCbll groups (81.8% and 84.6%) than in the L/Cbll/D and L/D groups (37.5% and 29.4%; P<0.001), while lacune numbers were lower in the L and L/LCbll groups (1.7±3.3 and 1.7±2.6) than in the L/Cbll/D and L/D groups (8.0±10.3 and 13.4±17.7, P=0.001). The L/LCbll group had more lobar cerebral microbleeds than the L group (93.2±121.8 versus 38.0±40.8, P=0.047). The lobar cerebellar group had a higher Aβ positivity (75% versus 28.6%, P=0.011) and lower lacune number (2.3±3.7 versus 8.6±1.2, P=0.041) than the dentate group.

Conclusions: Strictly lobar cerebral and cerebellar microbleeds are related to cerebral amyloid angiopathy, whereas any combination of concurrent lobar and deep microbleeds suggest hypertensive angiopathy regardless of cerebral or cerebellar compartments.

Keywords: cerebral amyloid angiopathy; hypertension; magnetic resonance imaging; risk factors; siderosis.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33198580/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : The SPID-GBA study: Sex distribution, Penetrance, Incidence, and Dementia in GBA-PD

The SPID-GBA study: Sex distribution, Penetrance, Incidence, and Dementia in GBA-PD

Abstract

Objective: To provide a variant-specific estimate of incidence, penetrance, sex distribution, and association with dementia of the 4 most common Parkinson disease (PD)-associated GBA variants, we analyzed a large cohort of 4,923 Italian unrelated patients with primary degenerative parkinsonism (including 3,832 PD) enrolled in a single tertiary care center and 7,757 ethnically matched controls.

Methods: The p.E326K, p.T369M, p.N370S, and p.L444P variants were screened using an allele-specific multiplexed PCR approach. All statistical procedures were performed using R or Plink v1.07.

Results: Among the 4 analyzed variants, the p.L444P confirmed to be the most strongly associated with disease risk for PD, PD dementia (PDD), and dementia with Lewy bodies (DLB) (odds ratio [OR] for PD 15.63, 95% confidence interval [CI] = 8.04-30.37, p = 4.97*10-16; OR for PDD 29.57, 95% CI = 14.07-62.13, p = 3.86*10-19; OR for DLB 102.7, 95% CI = 31.38-336.1, p = 1.91*10-14). However, an unexpectedly high risk for dementia was conferred by p.E326K (OR for PDD 4.80, 95% CI = 2.87-8.02, p = 2.12*10-9; OR for DLB 12.24, 95% CI = 4.95-30.24, p = 5.71*10-8), which, on the basis of the impact on glucocerebrosidase activity, would be expected to be mild. The 1.5-2:1 male sex bias described in sporadic PD was lost in p.T369M carriers. We also showed that PD penetrance for p.L444P could reach the 15% at age 75 years.

Conclusions: We report a large monocentric study on GBA-PD assessing mutation-specific data on the sex distribution, penetrance, incidence, and association with dementia of the 4 most frequent deleterious variants in GBA.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33209983/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Diagnostic and therapeutic biomarkers for Alzheimer's disease in human-derived platelets

Diagnostic and therapeutic biomarkers for Alzheimer's disease in human-derived platelets

Abstract

Background: Diagnosis of current Alzheimer's disease (AD) is difficult even for medical specialists, and there is no clear biomarker. Also, aging is highly related to the onset of AD.

Objectives: The purpose of this study is to screen miRNA as an aging-considered biomarker for AD treatment and diagnosis.

Methods: The patient group for this study was divided into a young normal, old normal, or AD group. We developed a method of discovering sequentially expressed miRNAs to distinguish miRNAs that were sequentially expressed in the three groups.

Results: Sequentially expressed miRNAs correlated highly with the patient's age, and most showed expression patterns that distinguished young, old, and AD. Specifically, the miRNA expression we found showed similar patterns in the brains of patients with AD. Among the selected miRNAs, one set derived from the same precursor: The expression of miR-150 was a disease- and age-specific downregulation in both 3p and 5p forms, and the precursor also had the same pattern. We named that triple matching. Also, the found miR-150 precursor had AD-specific miRNA-imbalance characteristics.

Conclusions: We developed a novel AD diagnostic method using triple matching and miRNA-imbalance. The triple matching and miRNA imbalance-based relative ratio diagnosis method we developed will be very powerful in resolving the challenges of absolute diagnostic quantification based on biomarker expression. Also, our research results suggest the possibility of a treatment target for AD.

Keywords: Alzheimer's disease; Arm switching; Biomarker; Micro RNA; Platelet.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33180258/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : The dietary inflammatory index (DII(R)) and its association with cognition, frailty, and risk of disabilities in older adults: A systematic review

The dietary inflammatory index (DII®) and its association with cognition, frailty, and risk of disabilities in older adults: A systematic review

Abstract

Background & aims: Systemic inflammation is considered an important issue in older adults and is associated with adverse health outcomes, such as frailty and cognitive impairment. Diet is a critical associated factor, and the dietary inflammatory index (DII®) is proposed as a promising tool to identify the association between diet and health outcomes. Our aims were: (i) to investigate the association between the DII® and frailty, cognition, and the consequent risk of disability in older adults; (ii) to discuss particularities of the use of DII® with older adults.

Methods: The research question was based on the PICOS strategy: Population = older adults; Intervention or Exposure = DII; Comparison = any comparator; Outcomes = frailty, cognition, and risk of disability; Type of study = cohort, cross-sectional or case-control studies. We searched publications in two electronic databases (PUBMED and Web of Science) up to May 20th, 2020.

Results: Seven studies met our criteria. Three investigated cognition (one cohort and two cross-sectional), and four investigated frailty or risk of disability (one cohort and three cross-sectional); none of the studies investigated both outcomes (frailty and cognition) simultaneously. The studies presented some issues, mainly concerning: (i) the collection of dietary data and calculation of the DII; (ii) the study design; (iii) calculation of the sample size; (iv) eligibility criteria; (v) time for follow-up; (vi) and choice of covariates.

Conclusion: despite the issues, the use of DII resulted in a significant association, or predictive value, with variables related to frailty and cognitive decline. Further studies, with sensitivity analysis of the different components of this index, are needed. DII showed to be a promising tool in the investigation of geriatric syndromes. This systematic review was registered in PROSPERO (CRD42020155672).

Keywords: Aging; Cognition; Dietary inflammatory index; Disabilities; Frailty.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33183575/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : The correlation of serum adiponectin and insulin resistance with the presence and severity of dementia in non-obese Alzheimer's patients

The correlation of serum adiponectin and insulin resistance with the presence and severity of dementia in non-obese Alzheimer's patients

Abstract

Background and aims: Alteration in the insulin signaling could contribute to the development of Alzheimer's disease (AD) through metabolic or inflammatory processes, adipokines could affect insulin dysregulation. This study aimed to investigate whether there is a correlation between serum adiponectin level alteration and insulin resistance with the presence and severity of AD, compared to normal controls.

Methods: This analytical observational study was conducted on 60 non-overweight and non-diabetic participants who were assigned to AD patients (n = 34) and healthy volunteers (n = 26). The diagnosis and severity of dementia were evaluated by the same protocol, and the Mini-Mental Score Exam (MMSE) questionnaire was utilized to collect the data. Moreover, adiponectin concentration, fasting blood sugar, and plasma insulin levels were measured using enzyme-linked immunosorbent assay. Furthermore, the homeostasis model assessment for insulin resistance (HOMA-IR) was utilized in this study.

Results: The mean ages of the AD patients and control participants were 71.35 and 70.46, respectively. In addition, the mean values of the serum adiponectin level of the participants were 9660 and 12,730 ng/mL in control and AD groups, respectively (P ≤ 0.05). Additionally, the insulin resistance (IR) was 2.90 and 5.10 in the control and AD groups, respectively (P ≤ 0.05). According to the results, there was a significant positive correlation between serum adiponectin level and HOMA-IR in the AD group; however, no significant correlation was observed between serum adiponectin level and MMSE score in this group. The MMSE score of AD patients significantly decreased by 1.2 times with an increase in each score of the IR (P ≤ 0.05).

Conclusion: A significant direct positive correlation was observed between the serum adiponectin level and IR among the AD patients. However, a significant decrease in cognition levels was detected following an increase in IR scores of the AD patients.

Keywords: Adiponectin; Alzheimer's disease; Insulin resistance; MMSE score.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33183566/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Synthesis of novel 4-methylthiocoumarin and comparison with conventional coumarin derivative as a multi-target-directed ligand in Alzheimer's disease

Synthesis of novel 4-methylthiocoumarin and comparison with conventional coumarin derivative as a multi-target-directed ligand in Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a multifactorial disorder characterized by cognitive deficit and memory loss. The pathological feature of the disease involves β-amyloid senile plaques, reduced levels of acetylcholine neurotransmitter, oxidative stress and neurofibrillary tangles formation within the brain of AD patients. The present study aims to screen the inhibitory activity of newly synthesized and existing novel 4-methylthiocoumarin derivative against acetylcholinesterase, butyrylcholinesterase, BACE1, β-amyloid aggregation and oxidative stress involved in the AD pathogenesis. The in vitro assays used in this study were Ellman's assay, FRET assays, Thioflavin T, transmission electron microscopy, circular dichroism, FRAP, and TEAC. Molecular docking and dynamics studies were performed to correlate the results. C3 and C7 (thiocoumarin derivatives) were found to be the most potent inhibitors of acetylcholinesterase (IC50-5.63 µM) and butyrylcholinesterase (IC50-3.40 µM) using Ellman's assays. Enzyme kinetic studies showed that C3 and C7 compounds followed by the mixed mode of inhibition using LB plot. C3 also moderately inhibited the BACE1 using FRET assay. C3 inhibited the fibrillization of β-amyloid peptides in a concentration-dependent manner as observed by Thioflavin T, TEM studies and Circular dichroism data. Molecular modeling studies were performed to understand the probable mode of binding of C3 and C7 in the binding pocket of acetylcholinesterase, butyrylcholinesterase, BACE1 and amyloid β peptides. This indicates the important role of hydrophobic interactions between C3 and acetylcholinesterase. C3 also exhibited significant antioxidant potential by FRAP and TEAC assays. Hence, C3 might serve as a promising lead for developing novel multi target-directed ligand for the treatment of AD.

Keywords: 4-Methylthiocoumarin derivative; Alzheimer's disease; BACE1 inhibitor; Cholinesterase inhibitor; In silico studies.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33184595/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Emergence of Barrel Motif in Amyloid-β Trimer: A Computational Study

Emergence of Barrel Motif in Amyloid-β Trimer: A Computational Study

Abstract

Amyloid-β (Aβ) peptides form assemblies that are pathological hallmarks of Alzheimer's disease. Aβ oligomers are soluble, mobile, and toxic forms of the peptide that act in the extracellular space before assembling into protofibrils and fibrils. Therefore, oligomers play an important role in the mechanism of Alzheimer's disease. Since it is difficult to determine by experiment the atomic structures of oligomers, which accumulate fast and are polymorphic, computer simulation is a useful tool to investigate elusive oligomers' structures. In this work, we report extended all-atom molecular dynamics simulations, both canonical and replica exchange, of Aβ(1-42) trimer starting from two different initial conformations: (i) the pose produced by the best docking of a monomer aside of a dimer (simulation 1), representing oligomers freshly formed by assembling monomers, and (ii) a configuration extracted from an experimental mature fibril structure (simulation 2), representing settled oligomers in equilibrium with extended fibrils. We showed that in simulation 1, regions with small β-barrels are populated, indicating the chance of spontaneous formation of domains resembling channel-like structures. These structural domains are alternative to those more representative of mature fibrils (simulation 2), the latter showing a stable bundle of C-termini that is not sampled in simulation 1. Moreover, trimer of Aβ(1-42) can form internal pores that are large enough to be accessed by water molecules and Ca2+ ions.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33180492/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Diazaspirononane Nonsaccharide Inhibitors of O-GlcNAcase (OGA) for the Treatment of Neurodegenerative Disorders

Diazaspirononane Nonsaccharide Inhibitors of O-GlcNAcase (OGA) for the Treatment of Neurodegenerative Disorders

Abstract

O-GlcNAcylation is a post-translational modification of tau understood to lower the speed and yield of its aggregation, a pathological hallmark of Alzheimer's disease (AD). O-GlcNAcase (OGA) is the only enzyme that removes O-linked N-acetyl-d-glucosamine (O-GlcNAc) from target proteins. Therefore, inhibition of OGA represents a potential approach for the treatment of AD by preserving the O-GlcNAcylated tau protein. Herein, we report the multifactorial optimization of high-throughput screening hit 8 to a potent, metabolically stable, and orally bioavailable diazaspirononane OGA inhibitor (+)-56. The human OGA X-ray crystal structure has been recently solved, but bacterial hydrolases are still widely used as structural homologues. For the first time, we reveal how a nonsaccharide series of inhibitors binds bacterial OGA and discuss the suitability of two different bacterial orthologues as surrogates for human OGA. These breakthroughs enabled structure-activity relationships to be understood and provided context and boundaries for the optimization of druglike properties.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33197187/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : The Role of Cholesterol in α-Synuclein and Lewy Body Pathology in GBA1 Parkinson's Disease

The Role of Cholesterol in α-Synuclein and Lewy Body Pathology in GBA1 Parkinson's Disease

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disease where dopaminergic neurons in the substantia nigra are lost, resulting in a decrease in striatal dopamine and, consequently, motor control. Dopaminergic degeneration is associated with the appearance of Lewy bodies, which contain membrane structures and proteins, including α-synuclein (α-Syn), in surviving neurons. PD displays a multifactorial pathology and develops from interactions between multiple elements, such as age, environmental conditions, and genetics. Mutations in the GBA1 gene represent one of the major genetic risk factors for PD. This gene encodes an essential lysosomal enzyme called β-glucocerebrosidase (GCase), which is responsible for degrading the glycolipid glucocerebroside into glucose and ceramide. GCase can generate glucosylated cholesterol via transglucosylation and can also degrade the sterol glucoside. Although the molecular mechanisms that predispose an individual to neurodegeneration remain unknown, the role of cholesterol in PD pathology deserves consideration. Disturbed cellular cholesterol metabolism, as reflected by accumulation of lysosomal cholesterol in GBA1-associated PD cellular models, could contribute to changes in lipid rafts, which are necessary for synaptic localization and vesicle cycling and modulation of synaptic integrity. α-Syn has been implicated in the regulation of neuronal cholesterol, and cholesterol facilitates interactions between α-Syn oligomers. In this review, we integrate the results of previous studies and describe the cholesterol landscape in cellular homeostasis and neuronal function. We discuss its implication in α-Syn and Lewy body pathophysiological mechanisms underlying PD, focusing on the role of GCase and cholesterol. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: autophagy; glycosphingolipid; lipid storage diseases; lysosomes; multilamellar bodies; neurodegeneration.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33219714/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Legumain Knockout Protects Against Aβ 1-42-Induced AD-like Cognitive Deficits and Synaptic Plasticity Dysfunction Via Inhibiting Neuroinflammation Without Cleaving APP

Legumain Knockout Protects Against Aβ 1-42-Induced AD-like Cognitive Deficits and Synaptic Plasticity Dysfunction Via Inhibiting Neuroinflammation Without Cleaving APP

Abstract

Neuroinflammation is the important pathological feature of Alzheimer's disease (AD). Legumain, a lysosomal cysteine protease, plays an important role in neuroinflammation during ischemic stroke and depressive disorder. Legumain is involved in AD process through cleaving APP; however, it is unclear if legumain can possibly modulate neuroinflammation without cleaving APP in AD. Thus, we established a mouse model of AD by single intracerebroventricular injections of Aβ1-42 in legumain knockout (KO) mice. The behavioral tests showed that legumain-KO effectively ameliorated cognitive impairment induced by Aβ1-42. Moreover, legumain deprivation significantly improves the synaptic plasticity damages in Aβ1-42-treated mice. Moreover, legumain-KO considerably inhibited the activation of microglia and reduced the expression of inflammatory cytokines in the hippocampus of Aβ1-42-treated mice. Interestingly, we found that legumain-KO inhibited TLR4/MyD88/NF-κB pathway, which was activated by Aβ1-42 in the hippocampus. In conclusion, our results suggested that legumain-KO reduced the level of neuroinflammation that was associated with inhibiting TLR4/MyD88/NF-κB pathways, thereby improving the hippocampal synaptic plasticity and reducing the cognitive impairments in Aβ1-42-treated mice. Legumain knockout blocked microglia activation by inhibiting TLR4/MyD88/NF-κB signaling pathways, and further reduced inflammatory cytokine expression. As a result, legumain knockout alleviated synaptic damage and cognitive impairment induced by Aβ1--42.

Keywords: Alzheimer's disease; Cognitions; Legumain; Neuroinflammation; Synaptic plasticity.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33219900/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.