A5080906950- Parkinson's Disease Mechanisms and Treatments
- RNA regulation and disease
- Neurological diseases and metabolism
- Amyotrophic Lateral Sclerosis Research
- Lysosomal Storage Disorders Research
- Neurogenetic and Muscular Disorders Research
- Genetic Neurodegenerative Diseases
- Nuclear Receptors and Signaling
- Alzheimer's disease research and treatments
- Cellular transport and secretion
- Neurological disorders and treatments
- MicroRNA in disease regulation
- Autism Spectrum Disorder Research
- RNA Research and Splicing
- Neuroinflammation and Neurodegeneration Mechanisms
- Autophagy in Disease and Therapy
- Genetic Associations and Epidemiology
- Cancer-related gene regulation
- Ginkgo biloba and Cashew Applications
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Pluripotent Stem Cells Research
- Neurotransmitter Receptor Influence on Behavior
- melanin and skin pigmentation
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2015-2024
Universitat de Barcelona
2014-2024
Hospital Clínic de Barcelona
2014-2024
Instituto de Salud Carlos III
2013-2024
Centro de Investigación Biomédica en Red
2013-2024
Biomedical Research Networking Center on Neurodegenerative Diseases
2014-2024
Instituto de Neurociencias
2023
University of North Dakota
2023
University of Michigan
2023
Genomics England
2021
Blood-cell-free circulating micro-RNAs (miRNAs) have been proposed as potential accessible biomarkers for neurodegenerative diseases such Parkinson's disease (PD). Here we analyzed the serum levels of 377 miRNAs in a discovery set 10 idiopathic (IPD) patients, PD patients carriers LRRK2 G2019S mutation (LRRK2 PD), and controls by using real-time quantitative PCR-based TaqMan MicroRNA arrays. We detected candidate differentially expressed miRNAs, which were further tested first validation...
The epigenomic landscape of Parkinson's disease (PD) remains unknown. We performed a genomewide DNA methylation and transcriptome studies in induced pluripotent stem cell (iPSC)-derived dopaminergic neurons (DAn) generated by reprogramming somatic skin cells from patients with monogenic LRRK2-associated PD (L2PD) or sporadic (sPD), healthy subjects. observed extensive changes DAn, RNA expression, which were common L2PD sPD. No significant differences present parental cells, undifferentiated...
Abstract Mitochondrial dysfunction has been implicated in the etiology of monogenic Parkinson’s disease (PD). Yet role that mitochondrial processes play most common form disease; sporadic PD, is yet to be fully established. Here, we comprehensively assessed function-associated genes PD by leveraging improvements scale and analysis GWAS data with recent advances our understanding genetics disease. We calculated a mitochondrial-specific polygenic risk score (PRS) showed cumulative small effect...
ABSTRACT Background Parkinson's disease (PD) associated with LRRK2 mutations has been described as similar to idiopathic PD minor clinical differences. No study compared the features of LRRK2‐ due different mutations. The objective this was compare ‐associated G2019S and G2385R each PD. Methods Sites within international Cohort Consortium undertook family‐based, community‐based, or clinic‐based studies gather data on manifesting carriers patients Results Five hundred sixteen mutation, 199...
We investigated the associations with HLA and microtubule-associated protein tau (
Objective In idiopathic Parkinson disease (IPD) sleep disorders are common and may antedate the onset of parkinsonism. Based on clinical similarities between IPD associated with LRRK2 gene mutations (LRRK2-PD), we aimed to characterize in parkinsonian nonmanifesting mutation carriers (NMC). Methods A comprehensive interview conducted by specialists, validated scales questionnaires, video-polysomnography followed multiple latency test (MSLT) assessed 18 LRRK2-PD (17 carrying G2019S one R1441G...
The Iberian Peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture neurodegenerative diseases.
Recently, we reported downregulated circulating levels of the microRNAs miR-19b, miR-29a, and miR-29c in Parkinson disease. Here investigated expression these serum samples from 56 patients with idiopathic rapid eye movement sleep behavior disorder, before after their conversion into a synucleinopathy. Compared to controls, found that level miR-19b is disorder antedates diagnosis disease dementia Lewy bodies 4.67 ± 2.61 years follow-up. Our findings indicate dysregulation microRNA occurs...
ABSTRACT Background: Asymptomatic, nonmanifesting carriers of leucine‐rich repeat kinase 2 mutations are at increased risk developing PD. Clinical and neuroimaging features may be associated with gene carriage and/or demarcate individuals greater for phenoconversion to Objectives: To investigate clinical dopamine transporter single‐photon emission computed tomography imaging characteristics asymptomatic carriers. Methods: A total 342 carriers' 259 noncarriers' relatives G2019S 2/PD patients...
Epidemiological studies have reported the co-occurrence of Parkinson disease (PD) and melanoma. Common genetic variants in MC1R (melanocortin 1 receptor) gene, which determines skin hair color, are associated with Here we investigated whether modulate risk PD by sequencing entire gene 870 patients 736 controls ascertained from Spain. We found that variant p.R160W (rs1805008) is marginally (odds ratio = 2.10, gender- age-adjusted p 0.009, Bonferroni-corrected 0.063). Our results suggest...
Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease characterized by the selective death of motor neurons in cortex, brain stem and spinal cord. Recently, missense variants angiogenin gene (ANG), an angiogenic factor expressed ventral horn that up-regulated hypoxia, have been found ALS patients Irish/Scottish, North American, Italian, French Dutch descent. To investigate role ANG German population, we screened for mutations sequencing entire coding region...
A reason for screening amyotrophic lateral sclerosis (ALS) patients mutations in the superoxide dismutase-1 (SOD1) gene is opportunity to find novel with properties that can give information on pathogenesis. c.352C>G (L117V) SOD1 mutation was found two Syrian ALS families living Europe. The disease showed unusually low penetrance and slow progression. In erythrocytes, total activity, as well specific activity of mutant protein, equal carriers family controls lacking mutations. structural...
Abstract Mutations in the PARK2 gene are associated with an autosomal recessive form of juvenile parkinsonism (AR-JP). These mutations affect parkin solubility and impair its E3 ligase activity, leading to a toxic accumulation proteins within susceptible neurons that results slow but progressive neuronal degeneration cell death. Here, we report RTP801/REDD1, pro-apoptotic negative regulator survival kinases mTOR Akt, is one such substrates. We observed knockdown elevated RTP801 sympathetic...
Parkinson's disease is associated with intracellular α-synuclein accumulation and ventral midbrain dopaminergic neuronal death in the Substantia Nigra of brain patients. The Rho GTPase pathway, mainly linking surface receptors to organization actin microtubule cytoskeletons, has been suggested participate pathogenesis. Nevertheless, its exact contribution remains obscure. To unveil participation family molecular pathogenesis disease, we first used C elegans demonstrate role small RAC1...
Recent evidence indicates a link between Parkinson's Disease (PD) and the expression of a-synuclein (SNCA) isoforms with different 3' untranslated regions (3'UTRs). Yet, post-transcriptional mechanisms regulating SNCA are unknown. Using large-scale in vitro /in silico screening we identified RNA-binding proteins (RBPs) that interact UTRs. We two RBPs, ELAVL1 TIAR, bind high affinity to most abundant translationally active UTR isoform (575 nt). Knockdown overexpression experiments indicate...
BackgroundBoth idiopathic and familial Parkinson's disease are associated with mitochondrial dysfunction. Mitochondria have their own DNA (mtDNA) previous studies reported that the release of mtDNA is a biomarker disease.MethodsWe now investigated relationship between replication, transcription in fibroblasts from patients (iPD) Leucine-rich repeat kinase 2G2019S -associated (LRRK2-PD), using Selfie-digital PCR, method allows absolute quantification genomes transcripts.FindingsIn comparison...
<h3>Background and Objectives</h3> Most patients with amyotrophic lateral sclerosis (ALS) lack a monogenic mutation. This study evaluates ALS cumulative genetic risk in an independent Michigan Spanish replication cohort using polygenic scores. <h3>Methods</h3> Participant samples from University of were genotyped assayed for the chromosome 9 open reading frame 72 hexanucleotide expansion. Final size was 219 223 healthy controls after genotyping participant filtering. Polygenic scores...