Raquel Real
A5000861365- Parkinson's Disease Mechanisms and Treatments
- Cellular transport and secretion
- Lysosomal Storage Disorders Research
- Neurological diseases and metabolism
- Neurological disorders and treatments
- Neurogenetic and Muscular Disorders Research
- Nuclear Receptors and Signaling
- Autism Spectrum Disorder Research
- RNA regulation and disease
- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Genetic Neurodegenerative Diseases
- Hereditary Neurological Disorders
- Biomedical and Engineering Education
- Amyotrophic Lateral Sclerosis Research
- Genetics, Bioinformatics, and Biomedical Research
- CNS Lymphoma Diagnosis and Treatment
- Pluripotent Stem Cells Research
- Diabetes Treatment and Management
- Botulinum Toxin and Related Neurological Disorders
- Neuroscience and Neural Engineering
- Studies on Chitinases and Chitosanases
- Cell Image Analysis Techniques
- Glioma Diagnosis and Treatment
University College London
2019-2025
National Hospital for Neurology and Neurosurgery
2019-2025
MRC London Institute of Medical Sciences
2024
Research Network (United States)
2021-2024
Imperial College London
2017-2024
King's College London
2024
University College Lahore
2023
UK Dementia Research Institute
2019
Universidade do Porto
2011-2018
Medical Research Council
2018
Parkinson's disease is a progressive neurodegenerative disorder with multifactorial causes, among which genetic risk factors play part. The RAB GTPases are regulators and substrates of LRRK2, variants in the LRRK2 gene important for disease. We aimed to explore variability within cases familial
Abstract Bi-allelic pathogenic variants in PRKN are the most common cause of autosomal recessive Parkinson’s disease (PD). 647 patients with -PD were included this international study. The present characterised and investigated for their effect on phenotype. Clinical features progression was also assessed. Among 133 index cases ( n = 582), there 58 (43.6%) structural variants, 34 (25.6%) missense, 20 (15%) frameshift, 10 splice site (7.5%%), 9 (6.8%) nonsense 2 (1.5%) indels. frequent...
Harnessing the potential of human stem cells for modeling physiology and diseases cortical circuitry requires monitoring cellular dynamics in vivo. We show that induced pluripotent cell (iPSC)-derived neurons transplanted into adult mouse cortex consistently organized large (up to ~100 mm3) vascularized neuron-glia territories with complex cytoarchitecture. Longitudinal imaging >4000 grafted developing revealed neuronal arbors refined via branch-specific retraction; synaptic networks...
Abstract Parkinson’s disease has a large heritable component and genome-wide association studies have identified over 90 variants with disease-associated common variants, providing deeper insights into the biology. However, there not been large-scale rare variant analyses for disease. To address this gap, we investigated genetic of at minor allele frequencies <1%, using whole genome exome sequencing data from 7184 cases, 6701 proxy cases 51 650 healthy controls Accelerating Medicines...
BackgroundPick's disease is a rare and predominantly sporadic form of frontotemporal dementia that classified as primary tauopathy. Pick's pathologically defined by the presence in frontal temporal lobes Pick bodies, composed hyperphosphorylated, three-repeat tau protein, encoded MAPT gene. has two distinct haplotypes, H1 H2; haplotype major genetic risk factor for four-repeat tauopathies (eg, progressive supranuclear palsy corticobasal degeneration), H2 protective these disorders. The aim...
Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder. Mendelian forms have revealed multiple genes, with notable emphasis on membrane trafficking; RAB GTPases play an important role in PD as subset are both regulators and substrates of LRRK2 kinase. To explore the PD, we undertook comprehensive examination their genetic variability familial PD.Methods: Affected probands from 130 multi-incident families underwent whole-exome sequencing genotyping, Potential...
Patients with Parkinson's disease (PD) have variable rates of progression. More accurate prediction progression could improve selection for clinical trials. Although some variance in can be predicted by age at onset and phenotype, we hypothesise that this further improved blood biomarkers.
Abstract Elucidating the genetic contributions to Parkinson’s disease (PD) etiology across diverse ancestries is a critical priority for development of targeted therapies in global context. We conducted largest sequencing characterization potentially disease-causing, protein-altering and splicing mutations 710 cases 11,827 controls from genetically predicted African or admixed ancestries. explored copy number variants (CNVs) runs homozygosity (ROHs) prioritized early onset familial cases....
Parkinson's disease (PD) affects millions of people worldwide, and up to 40% these patients develop dementia, profoundly affecting their quality life. Whether dementia (PDD) simply represents a late stage PD or constitutes distinct neurodegenerative process remains unresolved. To clarify this, we generated the largest single nuclear transcriptomic atlas PDD date - almost one million nuclei derived from anterior cingulate cortex inferior parietal lobule 64 post-mortem donors. By integrating...
An inversion polymorphism at the 17q21.31 locus defines H1 and H2 haplotypes, with former linked to multiple neurodegenerative disorders, including an increased risk of Parkinson's disease (PD). Although high linkage disequilibrium this has made it difficult decipher which gene(s) drive PD association, there is increasing evidence support role KANSL1 as a gene. been shown regulate expression some PD-associated genes pathways, likely part histone acetylating non-specific lethal (NSL) complex....
Abstract Background Pathogenic hexanucleotide repeat expansions in C9orf72 are the commonest genetic cause of frontotemporal dementia and/or amyotrophic lateral sclerosis. There is growing interest intermediate and their relationship to a wide range neurological presentations, including Alzheimer’s disease, Parkinson’s progressive supranuclear palsy, corticobasal degeneration, syndromes. Aims To assess prevalence large cohort prospectively-recruited patients clinically diagnosed with palsy...
Biallelic pathogenic variants in GBA1 are the cause of Gaucher disease (GD) type 1 (GD1), a lysosomal storage disorder resulting from deficient glucocerebrosidase. Heterozygous also common genetic risk factor for Parkinson's (PD). GD manifests with considerable clinical heterogeneity and is associated an increased PD.
Summary Background Parkinson’s disease (PD) is a progressive neurodegenerative disorder. Mendelian forms have revealed multiple genes, with notable emphasis on membrane trafficking; RAB GTPases play an important role in PD as subset are both regulators and substrates of LRRK2 protein kinase. To explore the PD, we undertook comprehensive examination their genetic variability familial PD. Methods Affected probands from 130 multi-incident families underwent whole-exome sequencing genotyping,...
There are 90 independent genome-wide significant genetic risk variants for Parkinson's disease (PD) but currently only five nominated loci PD progression. The biology of progression is likely to be central importance in defining mechanisms that can used develop new treatments. We studied 6766 patients, over 15,340 visits with a mean follow-up between 4.2 and 15.7 years carried out survival studies time motor endpoint, defined by reaching Hoehn Yahr stage 3 or greater, death (mortality). was...
The Parkinson's Families Project is a UK-wide study aimed at identifying genetic variation associated with familial and early-onset disease (PD). We recruited individuals clinical diagnosis of PD age motor symptom onset ≤45 years and/or family history in up to third-degree relatives. Where possible, we also affected unaffected analysed DNA samples combination single nucleotide polymorphism (SNP) array genotyping, multiplex ligation-dependent probe amplification (MLPA), whole-genome...
Mutations in the TANK-binding kinase 1 ( TBK1 ) gene have recently been shown to cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The phenotype is highly variable has associated with behavioral variant FTD, primary progressive aphasia, pure ALS. We describe clinical, anatomical, pathological features of a patient who developed corticobasal syndrome (CBS)/progressive nonfluent aphasia (PNFA) overlap. presented speech difficulties later an asymmetric akinetic–rigid...
Open science and collaboration are necessary to facilitate the advancement of Parkinson's disease (PD) research. Hackathons collaborative events that bring together people with different skill sets backgrounds generate resources creative solutions problems. These can be used as training networking opportunities, thus we coordinated a virtual 3-day hackathon event, during which 49 early-career scientists from 12 countries built tools pipelines focus on PD. Resources were created goal helping...
The genetic basis of Parkinson disease (PD) motor progression is largely unknown. Previous studies the genetics PD have included small cohorts and shown a limited overlap with risk factors from case-control studies. Here, we studied genomic variation associated severity early-stage in large longitudinal to help define biology potential new drug targets.
Abstract The genetic basis of levodopa-induced-dyskinesia (LiD) is poorly understood, and there have been few well-powered genome-wide studies. We performed a survival meta-analyses to study the effect variation on development LiD in five separate longitudinal cohorts, meta-analysed results. included 2784 PD patients, whom 14.6% developed LiD. found female sex (HR = 1.35, SE 0.11, P 0.007) younger age at onset 1.8, 0.14, 2 × 10 −5 ) increased probability developing identified three loci...
Abstract Up to 80% of Parkinson's disease patients develop dementia, but time dementia varies widely from motor symptom onset. Dementia with Lewy bodies presents clinical features similar Parkinson’s cognitive impairment precedes or coincides It remains controversial whether and are distinct conditions represent part a spectrum. The biological mechanisms underlying heterogeneity, in particular the development remain poorly understood, will likely be key understanding pathways and,...
Abstract Hereditary spastic paraplegia (HSP) is a group of heterogeneous inherited degenerative disorders characterized by lower limb spasticity. Fifty percent HSP patients remain yet genetically undiagnosed. The 100,000 Genomes Project (100KGP) large UK-wide initiative to provide genetic diagnosis previously undiagnosed and families with rare conditions. Over 400 were recruited the 100KGP. In order obtain diagnoses, gene-based burden testing was carried out for rare, predicted pathogenic...