A5006999330- Amyotrophic Lateral Sclerosis Research
- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Neurological diseases and metabolism
- Signaling Pathways in Disease
- Neurogenetic and Muscular Disorders Research
- RNA regulation and disease
- RNA Research and Splicing
- Conducting polymers and applications
- Neuropeptides and Animal Physiology
- Cell Image Analysis Techniques
- Prion Diseases and Protein Misfolding
- Glioma Diagnosis and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced Electron Microscopy Techniques and Applications
- Mitochondrial Function and Pathology
- Colorectal Cancer Screening and Detection
- Pluripotent Stem Cells Research
- Genetic Neurodegenerative Diseases
- Biochemical Acid Research Studies
- Histone Deacetylase Inhibitors Research
- Phagocytosis and Immune Regulation
- Cardiac Fibrosis and Remodeling
- Aging and Gerontology Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
University of Pennsylvania
2015-2024
Institute on Aging
2018-2024
Institute for Neurodegenerative Disorders
2017-2023
Bellvitge University Hospital
2011-2014
Institut d'Investigació Biomédica de Bellvitge
2011-2014
Universitat de Barcelona
2010-2013
Instituto de Neurologia Y Neurocirugia
2013
Anthrologica
2013
Centre for Biomedical Network Research on Rare Diseases
2007-2012
Centre for Genomic Regulation
2007-2012
MicroRNAs (miRNAs) are post-transcriptional gene expression regulators, playing key roles in neuronal development, plasticity and disease. Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by presence of protein inclusions or Lewy bodies a progressive loss dopaminergic neurons midbrain. Here, we have evaluated miRNA deregulation PD brain samples. MiRNA profiling revealed decreased miR-34b miR-34c areas with variable neuropathological affectation at...
Huntington disease (HD) is a neurodegenerative disorder that predominantly affects neurons of the forebrain. We have applied Illumina massively parallel sequencing to deeply analyze small RNA populations two different forebrain areas, frontal cortex (FC) and striatum (ST) healthy individuals with HD. More than 80% small-RNAs were annotated as microRNAs (miRNAs) in all samples. Deep revealed length sequence heterogeneity (IsomiRs) for vast majority miRNAs. Around 80–90% miRNAs presented...
Abstract The stereotypical distribution of TAR DNA-binding 43 protein (TDP-43) aggregates in frontotemporal lobar degeneration (FTLD-TDP) suggests that pathological TDP-43 spreads throughout the brain via cell-to-cell transmission and correlates with disease progression, but no vivo experimental data support this hypothesis. We first develop a doxycycline-inducible cell line expressing GFP-tagged cytoplasmic (iGFP-NLSm) as cell-based system to screen identify seeding activity human...
Abstract Despite the strong evidence linking transactive response DNA-binding protein 43 (TDP-43) aggregation to pathogenesis of frontotemporal lobar degeneration with TDP-43, amyotrophic lateral sclerosis and several neurodegenerative diseases, our knowledge sequence structural determinants its neurotoxicity remains incomplete. Herein, we present a new method for producing recombinant full-length TDP-43 filaments that exhibit morphological features similar those brain-derived filaments. We...
Huntington's disease (HD) is an autosomal dominantly inherited disorder caused by the expansion of CAG repeats in Huntingtin (HTT) gene. The abnormally extended polyglutamine HTT protein encoded has toxic effects. Here, we provide evidence to support that mutant interfere with cell viability at RNA level. In human neuronal cells, expanded exon-1 mRNA repeat lengths above threshold for complete penetrance (40 or greater) induced death and increased levels small CAG-repeated RNAs (sCAGs), ≈21...
Neurodegeneration in Alzheimer's disease (AD) is closely associated with the accumulation of pathologic tau aggregates form neurofibrillary tangles. We found that a p.Asp395Gly mutation VCP (valosin-containing protein) was dementia characterized neuropathologically by neuronal vacuoles and Moreover, appeared to exhibit disaggregase activity vitro, which impaired mutation. Additionally, intracerebral microinjection led increased mice knocked in, as compared injected wild-type mice. These...
Effective therapies are urgently needed to safely target TDP-43 pathology as it is closely associated with the onset and development of devastating diseases such frontotemporal lobar degeneration (FTLD-TDP) amyotrophic lateral sclerosis (ALS). In addition, present a co-pathology in other neurodegenerative Alzheimer's disease Parkinson's disease. Our approach develop TDP-43-specific immunotherapy that exploits Fc gamma-mediated removal mechanisms limit neuronal damage while maintaining...
Abstract TAR DNA-binding protein 43 (TDP-43) is an RNA binding found within ribonucleoprotein granules tethered to lysosomes via annexin A11. TDP-43 forms inclusions in many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with (FTLD–TDP) and limbic predominant age-related encephalopathy neuropathologic change (LATE-NC). Annexin A11 also known form aggregates ALS cases pathogenic variants ANXA11 . aggregation has not been described...
The Sox2 transcription factor is expressed early in the stem cells of blastocyst inner cell mass and, later, neural cells. We previously identified a 5'-regulatory region directing transgene expression to and precursors forebrain. Here, we identify core enhancer element able specify forebrain mouse embryos, show that same efficiently activates mass-derived embryonic (ES) Mutation POU binding sites, recognize factors Brn1 Brn2, shows these sites contribute activity are also essential for ES...
Previous studies have demonstrated the presence of hemoglobin α-chain and β-chain in neurons rodent human brain thus indicating that is a normal component nerve cells may play role intraneuronal oxyge
People with Down syndrome (DS) exhibit abnormal brain structure. Alterations affecting neurotransmission and signalling pathways that govern function are also evident. A large number of genes simultaneously expressed at levels in DS; therefore, it is a challenge to determine which gene(s) contribute specific abnormalities, then identify the key molecular involved. We generated RCAN1-TG mice study consequences RCAN1 over-expression investigate contribution phenotype DS. structural...
TAR-DNA binding protein-43 (TDP-43) proteinopathy is seen in multiple brain diseases. A standardized terminology was recommended recently for common age-related TDP-43 proteinopathy: limbic-predominant, encephalopathy (LATE) and the underlying neuropathological changes, LATE-NC. LATE-NC may be co-morbid with Alzheimer's disease changes (ADNC). However, there currently are ill-defined diagnostic classification issues among LATE-NC, ADNC, frontotemporal lobar degeneration (FTLD-TDP). practical...
Abstract Aim The heterogeneity in the distribution and morphological features of TAR DNA‐binding protein‐43 (TDP‐43) pathology brains frontotemporal lobar degeneration (FTLD‐TDP) patients their different clinical manifestations suggest that distinct pathological TDP‐43 strains could play a role this between FTLD‐TDP subtypes (A‐E). Our aim was to evaluate existence characterise specific seeding properties vitro vivo . Methods Results We used an inducible stable cell line expressing mutant...
Oxidative stress (OS) underlies neuronal dysfunction in many neurodegenerative disorders. Regulator of Calcineurin 1 (RCAN1 or DSCR1) is a dose-sensitive gene whose overexpression has been linked to Down syndrome (DS) and Alzheimer's disease (AD) neuropathology the response cells stimuli. Here, we show that RCAN1 mRNA protein expression are sensitive OS primary neurons, evaluate involvement dosage death induced by OS. We find Rcan1−/− neurons display an increased resistance damage H2O2,...
Genes located on chromosome 21, over-expressed in Down syndrome (DS) and Alzheimer's disease (AD) which regulate vesicle trafficking, are strong candidates for involvement AD neuropathology. Regulator of calcineurin activity 1 (RCAN1) is one such gene. We have generated mutant mice RCAN1 either (RCAN1ox) or ablated (Rcan1−/−) examined whether exocytosis from chromaffin cells, a classic cellular model neuronal exocytosis, altered using carbon fibre amperometry. find that Rcan1 regulates the...
MicroRNAs (miRNAs) and other small non-coding RNAs (sncRNAs) are post-transcriptional regulators of gene expression, playing key roles in neuronal development, plasticity, disease. Transcriptome deregulation caused by miRNA dysfunction has been associated to neurodegenerative diseases. Parkinson disease (PD) is the second most common showing coding transcriptome. On profiling sncRNA PD brain areas differently affected, we found that upregulation a vault RNA (svtRNA2-1a) widespread brains,...
TDP-43 is the major disease protein associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration ubiquitinated inclusions (FTLD-TDP). Here we identify transcriptional elongation factor Ell-a shared component of little complex (LEC) super (SEC)-as a strong modifier TDP-43-mediated neurodegeneration. Our data indicate select targets LEC SEC become upregulated in fly ALS/FTLD-TDP model. Among them, U12 snRNA stress-induced long non-coding RNA Hsrω, functionally...