A5079013457- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Alzheimer's disease research and treatments
- Botulinum Toxin and Related Neurological Disorders
- Peroxisome Proliferator-Activated Receptors
- Pancreatic function and diabetes
- Regulation of Appetite and Obesity
- Adipose Tissue and Metabolism
- Drug Transport and Resistance Mechanisms
- Lysosomal Storage Disorders Research
- Inflammatory Bowel Disease
- RNA regulation and disease
- Cellular transport and secretion
- Cell Adhesion Molecules Research
- Ginkgo biloba and Cashew Applications
- Diabetes Management and Research
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Signaling Pathways in Disease
- Immune Response and Inflammation
- Peptidase Inhibition and Analysis
- Adipokines, Inflammation, and Metabolic Diseases
- Cholesterol and Lipid Metabolism
- Diabetes Management and Education
Hamad bin Khalifa University
2020-2025
Qatar Foundation
2020-2025
Qatar Cardiovascular Research Center
2024
Biomedical Research Institute
2022
MRC Prion Unit
2022
University College London
2022
Amsterdam Neuroscience
2022
Amsterdam University Medical Centers
2022
Vrije Universiteit Amsterdam
2022
St Olav's University Hospital
2022
α-Synuclein (α-syn) phosphorylation at serine 129 (pS129–α-syn) is substantially increased in Lewy body disease, such as Parkinson’s disease (PD) and dementia with bodies (DLB). However, the pathogenic relevance of pS129–α-syn remains controversial, so we sought to identify when pS129 modification occurs during α-syn aggregation its role initiation, progression cellular toxicity disease. Using diverse assays, including real-time quaking-induced conversion (RT-QuIC) on brain homogenates from...
Robust biomarkers that can mirror Parkinson disease (PD) are of great significance. In this study, we present a novel approach to investigate disease-associated α-synuclein (αSyn) aggregates as PD clinical stage.We combined both seed amplification assay (SAA) and ELISA provide quantitative test readout reflects the severity patients with PD. To attain goal, initially explored potential our using 2 sets human brain homogenates (pilot validation sets) then verified it independent CSF cohorts;...
FK506-binding protein 51 (FKBP51) is a negative regulator of glucocorticoid receptor-α (GRα), although the mechanism unknown. We show here that FKBP51 also chaperone to peroxisome proliferator-activated receptor-γ (PPARγ), which essential for activity, and uncover underlying this differential regulation. In COS-7 cells, overexpression reduced GRα activity at response element-luciferase reporter, while increasing PPARγ proliferator element reporter. Conversely, FKBP51-deficient (knockout)...
Introduction HbA1c is a biomarker that plays an essential role in the diagnosis and follow-up of diabetic patients. The sensitivity specificity may be affected by common comorbidities seen individuals with diabetes mellitus, such as kidney affection, cardiac iron deficiency anemia, hemolytic hemoglobinopathies, drug consumption. Aim To assess control Diabetes Mellitus across different patient populations clinical scenarios. Methodology A quantitative research design to investigate impact...
Diagnosing α-synucleinopathies and assessing target engagement in trials is hindered by the lack of reliable biomarkers. Here, we introduce a first-in-kind quantitative, highly sensitive, disease-specific diagnostic assay, named Seeding Amplification ImmunoAssay (SAIA), developed validated to detect synucleinopathy-linked disorders. To this end, used wide range specimens, including 37 brain homogenates (BH) 559 cerebrospinal fluid (CSF) samples from subjects with diverse synucleinopathy...
Serological assays targeting antibodies against key viral proteins, including the Spike (S1), Receptor Binding Domain (RBD), and Nucleocapsid, play a critical role in understanding immunity supporting diagnostic efforts during COVID-19 pandemic, afterward. This study aimed to develop validate in-house for detecting anti-SARS-CoV-2 serum urine. ELISA-based assay was developed detect IgG IgM SARS-CoV-2. The examined urine samples of two different cohort patients affected by disease with...
Abstract Background DNA damage and repair (DDR) dysfunction are insults with broad implications for cellular physiology have been implicated in various neurodegenerative diseases. Alpha-synuclein (aSyn), a pre-synaptic nuclear protein associated disorders known as synucleinopathies, has double strand break (DSB) repair. However, although aSyn pathology observed cortical tissue of dementia Lewy body (DLB) cases, whether such coincides the occurrence not previously investigated. Moreover,...
Autism Spectrum Disorders (ASDs) are a group of neurodevelopmental disorders characterized by ritualistic-repetitive behaviors and impaired verbal non-verbal communication. Objectives were to determine the contribution genetic variation ASDs in Lebanese. Affymetrix Cytogenetics Whole-Genome 2.7 M CytoScan(™) HD Arrays used detect CNVs 41 Lebanese autistic children 35 non-autistic, developmentally delayed intellectually disabled patients. 33 normal participants as controls. 16 de novo 57...
Recent studies indicated that seeded fibril formation and toxicity of α-synuclein (α-syn) play a main role in the pathogenesis certain diseases including Parkinson's disease (PD), multiple system atrophy, dementia with Lewy bodies. Therefore, examination compounds abolish process seeding is considered key step towards therapy several synucleinopathies.Using biophysical, biochemical cell-culture-based assays, assessment eleven compounds, extracted from Chinese medicinal herbs, was performed...
Abstract Krabbe disease is an infantile neurodegenerative disorder resulting from pathogenic variants in the GALC gene that causes accumulation of toxic sphingolipid psychosine. are also associated with Lewy body diseases, umbrella term for age-associated diseases which protein α-synuclein aggregates into bodies. To explore whether has pathological similarities to disease, we performed observational post-mortem study brain tissue (n = 4) compared infant controls and identified widespread...
Nanobodies (Nbs), the single‐domain antigen‐binding fragments of dromedary heavy‐chain antibodies (HCAb), are excellent candidates as therapeutic and diagnostic tools in synucleinopathies because their small size, solubility stability. Here, we constructed an immune nanobody library specific to monomeric form alpha‐synuclein (α‐syn). Phage display screening allowed identification a nanobody, Nbα‐syn01, for α‐syn. Unlike previously developed nanobodies, Nbα‐syn01 recognized N‐terminal region...
The accumulation and aggregation of α-synuclein (α-syn) is the main pathologic event in Parkinson’s disease (PD), dementia with Lewy bodies, multiple system atrophy. α-Syn-seeded fibril formation its induced toxicity occupy a major role PD pathogenesis. Thus, assessing compounds that inhibit this seeding process considered key towards therapeutics synucleinopathies. Using biophysical biochemical techniques seeding-dependent cell viability assays, we screened total nine natural alkaloid...
Abstract Aggregation of the protein α‐synuclein (α‐syn) into insoluble intracellular assemblies termed Lewy bodies (LBs) is thought to be a critical pathogenic event in LB diseases such as Parkinson’s disease and dementia with LBs. In diseases, majority α‐syn phosphorylated at serine 129 (pS129), suggesting that this an important disease‐related post‐translational modification (PTM). However, PTMs do not typically occur isolation phosphorylation proximal tyrosine 125 (pY125) residue has...
The aggregation of α-synuclein (α-syn) into neurotoxic oligomers and fibrils is an important pathogenic feature synucleinopatheis, including Parkinson's disease (PD). A further characteristic PD the oxidative stress that results in formation aldehydes by lipid peroxidation. It has been reported brains deceased patients with contain high levels protein are cross-linked to these aldehydes. Increasing evidence also suggests prefibrillar oligomeric species more toxic than mature amyloid fibrils....
CEACAM1 promotes insulin extraction, an event that occurs mainly in liver. Phenocopying global Ceacam1 null mice (Cc1–/–), C57/BL6J fed a high-fat diet exhibited reduced hepatic levels and impaired clearance, followed by hyperinsulinemia, resistance visceral obesity. Conversely, forced liver-specific expression of protected sensitivity energy expenditure, limited gain total fat mass L-CC1 mice. Because protein is barely detectable white adipose tissue, we herein investigated whether...
Exenatide, a glucagon-like peptide-1 receptor agonist, induces insulin secretion. Its role in clearance has not been adequately examined. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes hepatic to maintain sensitivity. Feeding C57BL/6J mice high-fat diet down-regulates Ceacam1 transcription cause hyperinsulinemia, resistance, and steatosis, as null (Cc1-/- ). Thus, we tested whether exenatide regulates expression diet-fed this contributes its sensitizing effect....
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates insulin sensitivity by promoting hepatic clearance and mediating suppression of fatty acid synthase activity. Feeding C57BL/6J male mice with a high-fat (HF) diet for 3-4 weeks triggered >60% decrease in CEACAM1 levels to subsequently impair cause systemic resistance steatosis. This study aimed at investigating whether lipolysis drives reduction this constitutes key mechanism leading diet-induced metabolic...
Impairment of insulin clearance is being increasingly recognized as a critical step in the development resistance and metabolic disease. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes clearance. Null deletion or liver-specific inactivation Ceacam1 mice causes defect clearance, resistance, steatohepatitis, visceral obesity. Immunohistological analysis revealed reduction hepatic CEACAM1 obese subjects with fatty liver Thus, we aimed to determine whether this...
Abstract Synucleinopathies including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) are characterized by pathological accumulation of α-synuclein (α-syn). Amongst the various approaches attempting to tackle features synucleinopathies, antibody-based immunotherapy holds much promise. However, large size antibodies corresponding difficulty in crossing blood-brain barrier has limited development this area. To overcome issue, we engineered...