Lateral Sclerosis Research Articles

The causal association between epilepsy and amyotrophic lateral sclerosis: A two-sample Mendelian randomization study.

Epilepsy and amyotrophic lateral sclerosis (ALS) are common neurological disorders. The association between the two disorders has been raised in observational studies. However, it is uncertain to what extent they have mutual causal effects. In this study, we aimed to investigate their causal association using a two-sample Mendelian randomization (MR) method. We performed a two-sample bidirectional MR analysis to evaluate the causal association of epilepsy with the risk of ALS. Publicly published genome-wide association study statistics for epilepsy and ALS were used in the study. The primary analysis included genetic variants with a p value of less than 1 × 10-5 as instrumental variables. We applied several alternative methods, including inverse variance weighting, weighted median, simple mode, weighted mode, MR-Egger regression and MR pleiotropy residual sum and outlier, and statistical graphs to assess the associations of epilepsy and its subtype with the risk of ALS. Reverse MR analyses were also performed to examine the association of ALS with the risk of epilepsy. The primary MR analysis found no causal effect of epilepsy on risk of ALS (odds ration [OR]: 1.133, 95% confidence interval [CI]: 0.964-1.332, p=.130). Among subtypes of epilepsy, it also failed to observe any causal association between general epilepsy and ALS (OR: 1.036, 95% CI: 0.969-1.108, P=.300). However, focal epilepsy contributed to an increase in the risk of ALS (OR: 1.177, 95% CI: 1.027-1.348, p=.019). Moreover, the investigation of reverse causalities did not reveal significant results. The current study supports a causal influence of focal epilepsy on ALS risk. Future studies are needed to explore its potential role in ALS.

Genome-Wide and Transcriptome-Wide Association Studies on Northern New England and Ohio Amyotrophic Lateral Sclerosis Cohorts.

Amyotrophic lateral sclerosis (ALS) is an age-associated, fatal neurodegenerative disorder causing progressive paralysis and respiratory failure. The genetic architecture of ALS is still largely unknown. We performed a genome-wide association study (GWAS) and transcriptome-wide association study (TWAS) to understand genetic risk factors for ALS using a population-based case-control study of 435 ALS cases and 279 controls from Northern New England and Ohio. Single nucleotide polymorphism (SNP) genotyping was conducted using the Illumina NeuroChip array. Odds ratios were estimated using covariate-adjusted logistic regression. We also performed a genome-wide SNP-smoking interaction screening. TWAS analyses used PrediXcan to estimate associations between predicted gene expression levels across 15 tissues (13 brain tissues, skeletal muscle, and whole blood) and ALS risk. GWAS analyses identified the p.A382T missense variant (rs367543041, p = 3.95E-6) in the TARDBP gene, which has previously been reported in association with increased ALS risk and was found to share a close affinity with the Sardinian haplotype. Both GWAS and TWAS analyses suggested that ZNF235 is associated with decreased ALS risk. Our results support the need for future evaluation to clarify the role of these potential genetic risk factors for ALS and to understand genetic susceptibility to environmental risk factors.

Association between cerebrospinal fluid chitotriosidase level and amyotrophic lateral sclerosis: a systematic review.

One of the fatal and debilitating neurodegenerative diseases is amyotrophic lateral sclerosis (ALS). Increasing age is one of the risk factors of ALS. Considering that the elderly population in the world is increasing, it is very important to identify useful and effective diagnostic and treatment methods. The purpose of this systematic review is to determine the relationship between chitotriosidase (CHIT1) level and ALS disorder. Keywords "Amyotrophic Lateral Sclerosis", "Gehrig* Disease", "Charcot Disease", "Guam Disease", ALS, CHIT1 and chitotriosidase were searched in PubMed, Scopus, Web of Science and Science Direct databases without time limit on September 2023. Hundred twenty studies were obtained by searching, and finally, 14 studies were included in this study using the inclusion and exclusion criteria. In all 14 selected studies, the level of biomarker CHIT1 in the CSF of ALS patients was significantly higher than that of healthy control and disease control groups. But, in 8 studies that included 3 groups, no significant difference was observed between the CHIT1 levels in the two control groups. Six studies have reported the amount of CHIT1 level quantitatively. Among these 6 studies, in 5 studies CHIT1 level in disease control was higher than healthy control (not significant) and in only one study CHIT1 level was higher in healthy control compared to disease control (not significant). In all 14 studies, a multifold increase in CHIT1 levels has been observed in patients compared to healthy and disease control groups. Therefore, based on the findings of the studies, this study confirms the relationship between CHIT1 increase and ALS disorder.

Inhibition of RNA splicing triggers CHMP7 nuclear entry, impacting TDP-43 function and leading to the onset of ALS cellular phenotypes.

Amyotrophic lateral sclerosis (ALS) is linked to the reduction of certain nucleoporins in neurons. Increased nuclear localization of charged multivesicular body protein 7 (CHMP7), a protein involved in nuclear pore surveillance, has been identified as a key factor damaging nuclear pores and disrupting transport. Using CRISPR-based microRaft, followed by gRNA identification (CRaft-ID), we discovered 55 RNA-binding proteins (RBPs) that influence CHMP7 localization, including SmD1, a survival of motor neuron (SMN) complex component. Immunoprecipitation-mass spectrometry (IP-MS) and enhanced crosslinking and immunoprecipitation (CLIP) analyses revealed CHMP7's interactions with SmD1, small nuclear RNAs, and splicing factor mRNAs in motor neurons (MNs). ALS induced pluripotent stem cell (iPSC)-MNs show reduced SmD1 expression, and inhibiting SmD1/SMN complex increased CHMP7 nuclear localization. Crucially, overexpressing SmD1 in ALS iPSC-MNs restored CHMP7's cytoplasmic localization and corrected STMN2 splicing. Our findings suggest that early ALS pathogenesis is driven by SMN complex dysregulation.

A variant of the Hspa8 synaptic chaperone modifies disease in a SOD1G86R mouse model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a relatively common and invariably fatal, paralyzing motor neuron disease for which there are few treatment options. ALS is frequently associated with ubiquitin-positive motor neuronal aggregates, a pathology suggestive of perturbed proteostasis. Indeed, cellular chaperones, which are involved in protein trafficking and degradation often underlie familial ALS. Spinal muscular atrophy (SMA) is a second, common paralytic condition resulting from motor neuron loss and muscle atrophy. While SMA is now effectively treated, mechanisms underlying motor neuron degeneration in the disease remain far from clear. To address mechanistic questions about SMA, we recently identified a genetic modifier of the disease. The factor, a G470R variant in the constitutively expressed cellular chaperone, Hspa8, arrested motor neuron loss, prevented the abnormal accumulation of neurofilament aggregates at nerve terminals and suppressed disease. Hspa8 is best known for its role in autophagy. Amongst its many clients is the ALS-associated superoxide dismutase 1 (SOD1) protein. Given its suppression of the SMA phenotype, we tested potential disease-mitigating effects of Hspa8G470R in a mutant SOD1 mouse model of ALS. Unexpectedly, disease in mutant SOD1 mice expressing the G470R variant was aggravated. Motor performance of the mice deteriorated, muscle atrophy worsened, and lifespan shrunk even further. Paradoxically, SOD1 protein in spinal cord tissue of the mice was dramatically reduced. Our results suggest that Hspa8 modulates the ALS phenotype. However, rather than mitigating disease, the G470R variant exacerbates it.

Decreased diaphragm moving distance measured by ultrasound speckle tracking reflects poor prognosis in amyotrophic lateral sclerosis

ObjectiveDecreased cephalocaudal diaphragm movement may indicate respiratory dysfunction in amyotrophic lateral sclerosis (ALS). We aimed to evaluate diaphragm function in ALS using ultrasound speckle tracking, an image-analysis technology that follows similar pixel patterns. MethodsWe developed an offline application that tracks pixel patterns of recorded ultrasound video images using speckle-tracking methods. Ultrasonography of the diaphragm movement during spontaneous quiet respiration was performed on 19 ALS patients and 21 controls to measure the diaphragm moving distance (DMD) in the cephalocaudal direction during a single respiration. We compared respiratory function measures and analyzed the relationship between the clinical profiles and DMD. ResultsDMD was significantly lower in ALS patients than in the control group (0.6 ± 1.4 mm vs 2.2 ± 2.2 mm, p < 0.01) and positively correlated with phrenic nerve compound motor action potential amplitude (R = 0.63, p = 0.01). DMD was negatively correlated with the change in the ALS Functional Rating Scale-Revised scores per month after the exam (R = −0.61, p = 0.02), and those with a larger rate of decline had a significantly lower DMD (p = 0.03). ConclusionsDiaphragm ultrasound speckle tracking enabled the detection of diaphragm dysfunction in ALS. SignificanceDiaphragm ultrasound speckle tracking may be useful for predicting prognosis.

Ancient viral DNA in the human genome linked to neurodegenerative diseases

BackgroundHuman endogenous retroviruses (HERVs) are sequences in the human genome that originated from infections with ancient retroviruses during our evolution. Previous studies have linked HERVs to neurodegenerative diseases, but defining their role in aetiology has been challenging. Here, we used a retrotranscriptome-wide association study (rTWAS) approach to assess the relationships between genetic risk for neurodegenerative diseases and HERV expression in the brain, calculated with genomic precision. MethodsWe analysed genetic association statistics pertaining to Alzheimer’s disease, amyotrophic lateral sclerosis, multiple sclerosis, and Parkinson’s disease, using HERV expression models calculated from 792 cortical samples. Robust risk factors were considered those that survived multiple testing correction in the primary analysis, which were also significant in conditional and joint analyses, and that had a posterior inclusion probability above 0.5 in fine-mapping analyses. ResultsThe primary analysis identified 12 HERV expression signatures associated with neurodegenerative disease susceptibility. We found one HERV expression signature robustly associated with amyotrophic lateral sclerosis on chromosome 12q14 (MER61_12q14.2) and one robustly associated with multiple sclerosis on chromosome 1p36 (ERVLE_1p36.32a). A co-expression analysis suggested that these HERVs are involved in homophilic cell adhesion via plasma membrane adhesion molecules. ConclusionsWe found HERV expression profiles robustly associated with amyotrophic lateral sclerosis and multiple sclerosis susceptibility, highlighting novel risk mechanisms underlying neurodegenerative disease, and offering potential new targets for therapeutic intervention.

Causal association of circulating inflammatory proteins on neurodegenerative diseases: Insights from a mendelian randomization study.

Neuroinflammation is increasingly recognized as a pivotal factor in the development and progression of neurodegenerative disorders. While correlations between inflammatory cytokines and these diseases are documented, the definitive causal dynamics remain to be elucidated. We explored the causal association between 91 circulating inflammatory cytokines and Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Parkinson's disease (PD) through Mendelian randomization analysis. Leveraging genetic variants from the most comprehensive genome-wide association studies (GWAS) available for these cytokines, AD, ALS, MS and PD, we sought to uncover the causality. Our study validated a causal influence of genetically determined cytokine levels on the susceptibility to AD, with notable cytokines including C-X-C motif chemokine 1 (OR = 0.9993, p = 0.0424), Interleukin-18 (OR = 0.9994, p = 0.0186), Leukaemia inhibitory factor receptor (OR = 0.9993, p = 0.0122) and Monocyte chemoattractant protein-1 (OR = 0.9992, p = 0.0026) in risk attenuation. Additionally, a positive causal relationship was identified between two cytokines-C-C motif chemokine 19 (OR = 1.0005, p = 0.0478) and Fms-related tyrosine kinase 3 ligand (OR = 1.0005, p = 0.0210)-and AD incidence. Conversely, transforming growth factor-alpha (OR = 0.8630, p = 0.0298), CD40L receptor (OR = 0.7737, p = 1.1265E-09) and Interleukin-12 subunit beta (OR = 0.8987, p = 0.0333) showed inverse associations with ALS, MS and PD, respectively. The consistency observed in various MR analyses, alongside sensitivity analysis, underscored the absence of horizontal pleiotropy, thus supporting our causal findings. This study reveals, for the first time, a genetically anchored causal nexus between levels of circulating inflammatory cytokines and the risk of neurodegenerative diseases.

Differentially expressed lncRNAs in SOD1G93A mice skeletal muscle: H19, Myhas and Neat1 as potential biomarkers in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease characterized by progressive motor function and muscle mass loss. Despite extensive research in the field, the underlying causes of ALS remain incompletely understood, contributing to the absence of specific diagnostic and prognostic biomarkers and effective therapies. This study investigates the expression of long-non-coding RNAs (lncRNAs) in skeletal muscle as a potential source of biomarkers and therapeutic targets for the disease. The expression profiles of 12 lncRNAs, selected from the literature, were evaluated across different disease stages in tissue and muscle biopsies from the SOD1G93A transgenic mouse model of ALS. Nine out of the 12 lncRNAs were differentially expressed, with Pvt1, H19 and Neat1 showing notable increases in the symptomatic stages of the disease, and suggesting their potential as candidate biomarkers to support diagnosis and key players in muscle pathophysiology in ALS. Furthermore, the progression of Myhas and H19 RNA levels across disease stages correlated with longevity in the SOD1G93A animal model, effectively discriminating between long- and short-term survival individuals, thereby highlighting their potential as prognostic indicators. These findings underscore the involvement of lncRNAs, especially H19 and Myhas, in ALS pathophysiology, offering novel insights for diagnostic, prognostic and therapeutic targets.

Clinical characterization and founder effect analysis in Chinese amyotrophic lateral sclerosis patients with SOD1 common variants

Objective In the Asian population, SOD1 variants are the most common cause of amyotrophic lateral sclerosis (ALS). To date, more than 200 variants have been reported in SOD1. This study aimed to summarize the genotype–phenotype correlation and determine whether the patients carrying common variants derive from a common ancestor. Methods A total of 103 sporadic ALS (SALS) and 11 familial ALS (FALS) probands were included and variants were screened by whole exome sequencing. Functional analyses were performed on fibroblasts derived from patients with SOD1 p.V48A and control. Haplotype analysis was performed in the probands with p.H47R or p.V48A and their familial members. Results A total of 25 SOD1 variants were identified in 44 probands, in which p.H47R, p.V48A and p.C112Y variants were the most common variants. 94.3% and 60% of patients with p.H47R or p.V48A had lower limb onset with predominant lower motor neurons (LMNs) involvement. Patients with p.H47R had a slow progression and prolonged survival time, while patients with p.V48A exhibited a duration of 2–5 years. Patients with p.C112Y variant showed remarkable phenotypic variation in age at onset and disease course. SOD1V48A fibroblasts showed mutant SOD1 aggregate formation, enhanced intracellular reactive oxygen species level, and decreased mitochondrial membrane potential compared to the control fibroblast. Haplotype analysis showed that seven families had two different haplotypes. p.H47R and p.V48A variants did not originate from a common founder. Conclusions Our study expanded the understanding of the genotype–phenotype correlation of ALS with SOD1 variants and revealed that the common p.H47R or p.V48A variant did not have a founder effect.

The reliability and validity of in-person and remote behavioural screening tools for people with amyotrophic lateral sclerosis

ObjectiveThis study aimed to assess the psychometric properties of and relationships between total scores on different screening tools assessing behavioural change for people with amyotrophic lateral sclerosis (ALS), and whether administering the screens as online questionnaires (rather than on paper, in-person) influences total scores. MethodsThe behavioural component of the Edinburgh Cognitive and Behavioural ALS Screen (ECASb); the behavioural component of the ALS Cognitive Behavioural Screen (ALS-CBSb), the ALS-Frontotemporal Dementia Questionnaire (ALS-FTD-Q), the Beaumont Behavioural Inventory (BBI), and the Motor Neuron Disease Behavioural Instrument (MiND-B) were administered to 35 informants on paper. Online questionnaire versions of the behavioural screens were administered to 49 informants.Forward stepwise linear regressions were conducted to assess whether scores on behavioural screens were predicted by scores on the other behavioural screens and to assess whether total scores were predicted by the mode of administration (paper or online) of the screens. ResultsBehavioural screening tools, except the ECASb, had good internal consistency but mixed item-total correlations. All regression models assessing whether behavioural screen scores predict other behavioural screen scores were significant. The BBI performed best and the ECASb performed worst in terms of their predictive relationships with other screening tools. The administration mode of the questionnaires did not significantly affect total scores. ConclusionsThe psychometric properties of the scales varied. The scales predicted each other's scores, supporting convergent validity. Online and paper versions performed similarly, and demographics did not predict scores.

Living systematic review and comprehensive network meta-analysis of ALS clinical trials: study protocol.

Amyotrophic lateral sclerosis (ALS) is a fatal neurogenerative disease with no effective treatment to date. Despite numerous clinical trials, the majority of studies have been futile in their effort to significantly alter the course of the disease. However, these studies may still provide valuable information for identifying patient subgroups and generating new hypotheses for future research. Additionally, synthesising evidence from these studies may help overcome the limitations of individual studies. Network meta-analysis may refine the assessment of efficacy in specific patient subgroups, evaluate intervention characteristics such as mode of administration or biological mechanisms of action, and rank order promising therapeutic areas of interest. Therefore, we aim to synthesise the available evidence from ALS clinical trials. We will conduct a systematic review to identify all clinical trials that assessed disease-modifying pharmaceutical therapies, cell therapies, or supplements in patients with ALS. Outcomes of interest are clinical disease progression outcomes and survival. We will conduct this search in the period Q4 2024 in three databases: PubMed, Embase and ClinicalTrials.gov for studies from 1999 to 2023. Individual patient data and aggregate data will be collected and subsequentially synthesised in meta-analytical models. The final model will be presented as an open-source web application with biannual updates of the underlying data, thereby providing a 'living' overview of the ALS clinical trial landscape. No ethics approvals are required. Findings will be presented at relevant conferences and submitted to peer-reviewed journals. Data will be stored anonymously in secure repositories.

Bisdemethoxycurcumin, a novel potent polyphenolic compound, effectively inhibits the formation of amyloid aggregates in ALS-associated hSOD1 mutant (L38R)

Protein misfolding is a biological process that leads to protein aggregation. Anomalous misfolding and aggregation of human superoxide dismutase (hSOD1) into amyloid aggregates is a characteristic feature of amyotrophic lateral sclerosis (ALS), a neurodegenerative illness. Thus, focusing on the L38R mutant may be a wise decision to comprehend the SOD1 disease process in ALS. We suggest that Bisdemethoxycurcumin (BDMC) may be a strong anti-amyloidogenic polyphenol against L38R mutant aggregation. Protein stability, hydrophobicity, and flexibility were altered when BDMC was bound to the L38R mutant, as shown by molecular dynamic (MD) simulations and molecular docking. FTIR data shows α-Helix dominance in BDMC-containing samples, with reduced β-sheet and disordered peaks, indicating the decrease of aggregate species. ThT aggregation kinetics curves show BDMC reduces L38R mutant aggregation dose-dependently, with higher BDMC concentrations yielding greater reductions. TEM images showed various quantities of amorphous aggregates, but notably, 60 μM BDMC markedly reduced aggregate density, underscoring BDMC's inhibitory effect. Hemolysis tests revealed aggregate species in BDMC-treated samples were less toxic than in L38R mutant samples alone at the same concentrations and exposure times. Overall, BDMC has substantial potential to develop highly effective inhibitors that mitigate the risk of fatal ALS.

CNN-Based Neurodegenerative Disease Classification Using QR-Represented Gait Data.

The primary aim of this study is to develop an effective and reliable diagnostic system for neurodegenerative diseases by utilizing gait data transformed into QR codes and classified using convolutional neural networks (CNNs). The objective of this method is to enhance the precision of diagnosing neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Huntington's disease (HD), through the introduction of a novel approach to analyze gait patterns. The research evaluates the CNN-based classification approach using QR-represented gait data to address the diagnostic challenges associated with neurodegenerative diseases. The gait data of subjects were converted into QR codes, which were then classified using a CNN deep learning model. The dataset includes recordings from patients with Parkinson's disease (n = 15), Huntington's disease (n = 20), and amyotrophic lateral sclerosis (n = 13), and from 16 healthy controls. The accuracy rates obtained through 10-fold cross-validation were as follows: 94.86% for NDD versus control, 95.81% for PD versus control, 93.56% for HD versus control, 97.65% for ALS versus control, and 84.65% for PD versus HD versus ALS versus control. These results demonstrate the potential of the proposed system in distinguishing between different neurodegenerative diseases and control groups. The results indicate that the designed system may serve as a complementary tool for the diagnosis of neurodegenerative diseases, particularly in individuals who already present with varying degrees of motor impairment. Further validation and research are needed to establish its wider applicability.

Metabolomics of basal tears in amyotrophic lateral sclerosis: a cross-sectional study

PurposeAmyotrophic lateral sclerosis (ALS) clinical variability, along with the lack of conclusive diagnostic instruments, result in average diagnosis delays of 9 months. This study aimed to assess whether metabolomic profiling of basal tears in ALS patients could act as a biological marker for diagnosing ALS, predicting prognosis, and discriminating between endophenotypes. MethodsA single-center prospective case-control study was conducted in France from September 2021 to March 2023 including patients with ALS according to the revised EI Escorial criteria. Two microliters of basal tears were collected using microcapillary glass tubes and analyzed with ultra-high performance liquid chromatography coupled with mass spectrometry. Both univariate and multivariate analyses were performed. ResultsTwenty-five patients with ALS and 30 controls were included. No significant differences in metabolite levels were found between ALS and control groups (p>0.05). The basal tear metabolome significantly discriminated bulbar and spinal forms of ALS based on 6 metabolites, among which 5 were decreased (aniline, trigonelline, caffeine, theophylline and methyl beta-D-galactoside) in the bulbar form and 1 was decreased in the spinal form (dodecanedioic acid). ConclusionThis study represents the first prospective analysis of basal tear metabolomics in individuals with ALS. Despite the inability to distinguish between ALS patients and controls based on metabolic signatures, these findings could contribute to understanding the phenotypic diversity of ALS. Notably, distinct metabolic profiles were identified that differentiate between the bulbar and spinal forms of the disease.

A simplified and safe approach to percutaneous endoscopic gastrostomy tube placement in amyotrophic lateral sclerosis (ALS) patients

A simplified and safe approach to percutaneous endoscopic gastrostomy tube placement in amyotrophic lateral sclerosis (ALS) patients

End-of-Life and Hospice Care in Neurologic Diseases.

The care of a patient with neurologic disease at end-of-life requires expertise in addressing advance care planning, hospice, symptom management, and caregiver support. Neurologists caring for patients with advanced neurologic disease often identify changes in disease trajectory, functional status, or goals of care that prompt discussions of advance care planning and hospice. Patients nearing end-of-life may develop symptoms such as dyspnea, secretions, delirium, pain, and seizures. Neurologists may be the primary clinicians managing these symptoms, particularly in the hospitalized patient, though they may also lend their expertise to non-neurologists about expected disease trajectories and symptoms in advanced neurologic disease. This article aims to help neurologists guide patients and caregivers through the end-of-life process by focusing on general knowledge that can be applied across diseases as well as specific considerations in severe stroke and traumatic brain injury, amyotrophic lateral sclerosis, Parkinson's disease, and dementia.

Phytochemicals as substances that affect astrogliosis and their implications for the management of neurodegenerative diseases.

Astrocytes are a multifunctional subset of glial cells that are important in maintaining the health and function of the central nervous system (CNS). Reactive astrocytes may release inflammatory mediators, chemokines, and cytokines, as well as neurotrophic factors. There may be neuroprotective (e.g., cytokines, like IL-6 and TGF-b) and neurotoxic effects (e.g., IL-1β and TNF-a) associated with these molecules. In response to CNS pathologies, astrocytes go to a state called astrogliosis which produces diverse and heterogenic functions specific to the pathology. Astrogliosis has been linked to the progression of many neurodegenerative disorders. Phytochemicals are a large group of compounds derived from natural herbs with health benefits. This review will summarize how several phytochemicals affect neurodegenerative diseases (e.g., Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, and Parkinson's disease) in basic medical and clinical studies and how they might affect astrogliosis in the process.

Real-Time Home Automation System Using BCI Technology.

A Brain-Computer Interface (BCI) processes and converts brain signals to provide commands to output devices to carry out certain tasks. The main purpose of BCIs is to replace or restore the missing or damaged functions of disabled people, including in neuromuscular disorders like Amyotrophic Lateral Sclerosis (ALS), cerebral palsy, stroke, or spinal cord injury. Hence, a BCI does not use neuromuscular output pathways; it bypasses traditional neuromuscular pathways by directly interpreting brain signals to command devices. Scientists have used several techniques like electroencephalography (EEG) and intracortical and electrocorticographic (ECoG) techniques to collect brain signals that are used to control robotic arms, prosthetics, wheelchairs, and several other devices. A non-invasive method of EEG is used for collecting and monitoring the signals of the brain. Implementing EEG-based BCI technology in home automation systems may facilitate a wide range of tasks for people with disabilities. It is important to assist and empower individuals with paralysis to engage with existing home automation systems and gadgets in this particular situation. This paper proposes a home security system to control a door and a light using an EEG-based BCI. The system prototype consists of the EMOTIV Insight™ headset, Raspberry Pi 4, a servo motor to open/close the door, and an LED. The system can be very helpful for disabled people, including arm amputees who cannot close or open doors or use a remote control to turn on or turn off lights. The system includes an application made in Flutter to receive notifications on a smartphone related to the status of the door and the LEDs. The disabled person can control the door as well as the LED using his/her brain signals detected by the EMOTIV Insight™ headset.

Natural Compounds as Inhibitors of Aβ Peptide and Tau Aggregation.

Neurodegenerative conditions like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) encompass disorders characterized by the degeneration of neurons in specific circumstances. The quest for novel agents to influence these diseases, particularly AD, has unearthed various natural compounds displaying multifaceted activities and diverse pharmacological mechanisms. Given the ongoing extensive study of pathways associated with the accumulation of neurofibrillary aggregates and amyloid plaques, this paper aims to comprehensively review around 130 studies exploring natural products. These studies focus on inhibiting the formation of amyloid plaques and tau protein tangles, with the objective of potentially alleviating or delaying AD.