A5078935672- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Genetic Neurodegenerative Diseases
- Parkinson's Disease Mechanisms and Treatments
- RNA Research and Splicing
- biodegradable polymer synthesis and properties
- Marine animal studies overview
- RNA and protein synthesis mechanisms
- Alzheimer's disease research and treatments
- Vestibular and auditory disorders
- Hearing, Cochlea, Tinnitus, Genetics
Johns Hopkins University
2025
Thomas Jefferson University
2021-2024
Jefferson Hospital for Neuroscience
2022
Abstract A G4C2 hexanucleotide repeat expansion in the C9orf72 gene is most common genetic cause of ALS and FTLD (C9-ALS/FTLD) with cytoplasmic TDP-43 inclusions observed regions neurodegeneration. The accumulation repetitive RNAs dipeptide protein (DPR) are two proposed mechanisms toxicity C9-ALS/FTLD linked to impaired nucleocytoplasmic transport. Nucleocytoplasmic transport regulated by phenylalanine-glycine nucleoporins (FG nups) that comprise nuclear pore complex (NPC) permeability...
Vestibular hair cells (HCs) faithfully and rapidly detect head motions gravity, driving motor reflexes that stabilize balance gaze during locomotion. With the transition from water to land, amniote vestibular inner ear added type I HCs, which differ II HCs anamniote by their large calyx afferent synapse, non-quantal transmission, a large, low-voltage-activated K+ conductance (g K,L ). We recently showed both g major conductances (A-type delayed rectifier) require K V 1.8 ( Kcna10 ) subunits....
Abstract Translation of the hexanucleotide G4C2 expansion associated with C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) produces five different dipeptide repeat protein (DPR) species that can confer toxicity. There is yet much to learn about contribution a single DPR disease pathogenesis. We show here short length sufficient for poly-GR neurotoxicity in vitro, phenomenon previously unobserved. This toxicity also reported vivo our novel knock-in mouse model...
Abstract Expanded intronic G 4 C 2 repeats in the C9ORF72 gene cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These are translated through a non-AUG-dependent mechanism into five different dipeptide repeat proteins (DPRs), including poly-glycine-arginine (GR), which is aggregation-prone neurotoxic. Here, we report that Kapβ2 GR interact, co-aggregating, cultured neurons in-vitro CNS tissue in-vivo. Importantly, this interaction significantly decreased risk of...
Summary Expanded intronic G 4 C 2 repeats in the C9orf72 gene cause several cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These are translated through a non-AUG-dependent mechanism into five different dipeptides (DPRs), including poly-glycine-arginine (GR), which is aggregation-prone eventually neurotoxic. Here, we report that Kapβ2 GR interact, co-aggregating primary neurons in-vitro CNS tissue in-vivo . Importantly, this interaction improves overall...
Abstract Translation of the hexanucleotide G4C2 expansion associated with C9orf72 Amyotrophic Lateral Sclerosis and Frontotemporal Dementia (ALS/FTD) produces five different dipeptide repeat protein (DPR) species that can confer toxicity. There is yet much to learn about contribution a single DPR disease pathogenesis. We show here short length sufficient for poly-GR neurotoxicity in vitro, phenomenon previously unobserved. This toxicity also reported vivo our novel knock-in mouse model...
Abstract Amyotrophic lateral sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD) share clinical, neuropathological, genetic features. This includes common disease-causing mutations such as the expanded G4C2 repeat in C9orf72 gene (C9-ALS/FTLD) cytoplasmic insoluble protein depositions of TDP-43 degenerating regions brain spinal cord. Proposed mechanisms toxicity C9-ALS/FTLD are production expansion transcripts their dipeptide proteins (DPRs) products which hypothesized to drive...
Abstract Background: Translation of the hexanucleotide G4C2 expansion associated with C9orf72 Amyotrophic Lateral Sclerosis and Frontotemporal Dementia (ALS/FTD) produces five different dipeptide repeat protein (DPR) species that can confer toxicity. Yet, there is much to learn about contribution DPRs disease pathogenesis, as not all function localize within cells in same manner, nor are they length. These phenomena create a heterogeneity confounds study their toxic consequences. Methods: In...