A5082361223- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- RNA Research and Splicing
- RNA modifications and cancer
- Cancer-related gene regulation
- RNA regulation and disease
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Nuclear Receptors and Signaling
- biodegradable polymer synthesis and properties
- Macrophage Migration Inhibitory Factor
- Synthetic Organic Chemistry Methods
- Wastewater Treatment and Nitrogen Removal
- Prion Diseases and Protein Misfolding
- Apelin-related biomedical research
- Circular RNAs in diseases
- Histone Deacetylase Inhibitors Research
- Genetic Neurodegenerative Diseases
Western University
2013-2024
Pontificia Universidad Católica de Chile
2011-2013
Abstract Background Amyotrophic Lateral Sclerosis (ALS) is a progressive, adult onset, fatal neurodegenerative disease of motor neurons. There emerging evidence that alterations in RNA metabolism may be critical the pathogenesis ALS. MicroRNAs (miRNAs) are small non-coding RNAs key determinants mRNA stability. Considering miRNAs increasingly being recognized as having role variety diseases, we decided to characterize miRNA expression profile spinal cord (SC) tissue sporadic ALS (sALS) and...
Abstract Aggregation of the RNA-binding protein TAR DNA binding (TDP-43) is a hallmark TDP-proteinopathies including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). As TDP-43 aggregation dysregulation are causative neuronal death, there special interest in targeting this as therapeutic approach. Previously, we found that extensively co-aggregated with dual function GEF (guanine exchange factor) rho guanine nucleotide factor (RGNEF) ALS patients. Here, show an...
Neurofilaments (NFs) are the most abundant cytoskeletal component of vertebrate myelinated axons. NFs function by determining axonal caliber, promoting growth and forming a 3-dimensional lattice that supports organization cytoplasmic organelles. The stoichiometry NF protein subunits (NFL, NFM NFH) has to be tightly controlled avoid formation neuronal inclusions (NCIs), degeneration death, all pathological hallmarks amyotrophic lateral sclerosis (ALS). post-transcriptional control transcripts...
While most human genes express mRNA 3′ untranslated region (3′ UTR) variants of different lengths, their impact on cell physiology and disease remains largely unknown. Here, we studied UTR length heterogeneity in amyotrophic lateral sclerosis (ALS) determined that three ALS-linked transcripts exhibit lengthening UTRs patient samples. We investigated phenotypical effects a neuronal line expressing these observed expression unique 3′s induces morphological changes at levels. Among the...
Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive motor neuron degeneration and neurofilament aggregate formation. Spinal neurons in ALS also show selective suppression the levels of low molecular weight (NEFL) mRNA. We have been interested investigating role microRNAs (miRNAs) NEFL transcript stability. MiRNAs are small, 20-25 nucleotide, non-coding RNAs that act as post-transcriptional gene regulators targeting 3' untranslated region (3'UTR) mRNA resulting...
Rho guanine nucleotide exchange factor (RGNEF) is a novel NFL mRNA destabilizing that forms neuronal cytoplasmic inclusions in spinal motor neurons both sporadic (SALS) and familial (FALS) ALS patients. Given the observation of genetic mutations number binding proteins associated with ALS, including TDP-43, FUS/TLS mtSOD1, we analysed ARHGEF28 gene (approx. 316 kb) encodes for RGNEF FALS cases to determine if were present. We performed genomic sequencing, copy variation analysis using TaqMan...
Abstract Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease with no known etiology. The formation of pathological protein inclusions, including RNA-binding proteins such as TDP-43 and rho guanine nucleotide exchange factor (RGNEF) are hallmark ALS. Despite intensive research, the mechanisms behind aggregate in ALS remains unclear. We have investigated role metabolic stress analyzing how it relevant to co-aggregation observed between RGNEF motor neurons...
MicroRNAs (miRNAs) are small non-coding RNAs that regulate the majority of transcriptome at a post-transcriptional level. Because this critical role, it is important to ensure assays used determine their functionality robust and reproducible. Typically, reporter gene assay in cell-based systems has been first-line method study miRNA functionality. In order overcome some potential errors interpretation can be associated with assay, we have developed detailed protocol for luciferase modified...
TAR DNA-binding protein 43 (TDP-43) is a DNA/RNA-binding that integral to RNA processing. Among these functions critical role in microRNA (miRNA) biogenesis through interactions with the DROSHA and DICER complexes. It has been previously shown there general reduction miRNA levels within spinal cord motor neurons of amyotrophic lateral sclerosis (ALS) patients. In addition, most common pathological feature ALS re-distribution TDP-43 from nucleus cytoplasm where it forms cytoplasmic...
Common pathological features of amyotrophic lateral sclerosis (ALS) include cytoplasmic aggregation several RNA-binding proteins. Out these proteins, TDP-43, FUS/TLS and RGNEF have been shown to co-aggregate with one another within motor neurons sporadic ALS (sALS) patients, suggesting that there may be a common regulatory network disrupted. MiRNAs recent focus in research as they identified globally down-regulated the spinal cord patients. The objective this study was identify if are...
Paraspeckles are nuclear condensates formed by NEAT1_2 lncRNA and different RNA-binding proteins. In general, these membraneless organelles function in the regulation of gene expression translation miRNA processing, doing this, they regulate cellular homeostasis mediate pro-survival cell. Despite evidence showing importance paraspeckles stress response, dynamics their components under conditions osmotic remain unknown. We exposed HEK293T cells to sorbitol examined using real-time PCR....
Background and purpose Previous studies have suggested that elevated progesterone levels are associated with a slower disease course in amyotrophic lateral sclerosis ( ALS ). Given the effects of mediated part by classical receptor PR ), expression cellular localization A B isoforms ‐A ‐B, respectively) control (neuropathologically normal) ‐affected spinal cord SC ) were examined. Methods Semi‐quantitative RT ‐ PCR , immunohistochemistry immunofluorescence analyses cervical lumbar...