A5072055814- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Neurological disorders and treatments
- Parkinson's Disease Mechanisms and Treatments
- Muscle Physiology and Disorders
- Genetics and Neurodevelopmental Disorders
- Phosphodiesterase function and regulation
- Receptor Mechanisms and Signaling
- Alzheimer's disease research and treatments
- Ubiquitin and proteasome pathways
- Neuroscience and Neuropharmacology Research
- Neuroscience of respiration and sleep
- Ion channel regulation and function
- RNA Research and Splicing
- Cellular transport and secretion
- Hereditary Neurological Disorders
- Signaling Pathways in Disease
- Protein Kinase Regulation and GTPase Signaling
- Neuropeptides and Animal Physiology
- Functional Brain Connectivity Studies
- Neurological diseases and metabolism
- Nerve injury and regeneration
- RNA regulation and disease
- Advanced MRI Techniques and Applications
- Botulinum Toxin and Related Neurological Disorders
Johns Hopkins University
2015-2025
Johns Hopkins Medicine
2015-2025
Chapman University
2020-2023
Behavioral Pharma (United States)
2022
Flinders Medical Centre
2014-2022
Charing Cross Hospital
2020
Imperial College Healthcare NHS Trust
2020
VA Healthcare-VISN 4
2019
VA Pittsburgh Healthcare System
2019
University of Pittsburgh
2015-2019
Huntington's disease (HD) is one of an increasing number human neurodegenerative disorders caused by a CAG/polyglutamine-repeat expansion. The mutation occurs in gene unknown function that expressed wide range tissues. molecular mechanism responsible for the delayed onset, selective pattern neuropathology, and cell death observed HD has not been described. We have mice transgenic exon 1 carrying (CAG)115 to (CAG)156 repeat expansions develop pronounced neuronal intranuclear inclusions,...
Mutations in the leucine-rich repeat kinase 2 gene ( LRRK2 ) cause late-onset Parkinson's disease (PD) with a clinical appearance indistinguishable from idiopathic PD. Initial studies suggest that mutations are most common yet identified determinant of PD susceptibility, transmitted an autosomal-dominant mode inheritance. Herein, we characterize and transcript human brain subclone predominant ORF. Exogenously expressed protein migrates at ≈280 kDa is present largely cytoplasm but also...
Expanded polyglutamine repeats have been proposed to cause neuronal degeneration in Huntington's disease (HD) and related disorders, through abnormal interactions with other proteins containing short tracts such as the transcriptional coactivator CREB binding protein, CBP. We found that CBP was depleted from its normal nuclear location present aggregates HD cell culture models, transgenic mice, human postmortem brain. specifically interfere CBP-activated gene transcription, overexpression of...
The neurodegenerative diseases Huntington disease, dentatorubropallidoluysian atrophy, spinocerebellar atrophy type 3, and spinal bulbar muscular are caused by expansion of a polyglutamine tract within their respective gene products. There is increasing evidence that generation truncated proteins containing an expanded may be key step in the pathogenesis these disorders. We now report that, similar to huntingtin, atrophin-1, ataxin-3, androgen receptor cleaved apoptotic extracts....
Abstract Anterograde, retrograde, and combined axonal transport methods were used to describe the descending efferent projections of a region rostral ventrolateral medullary reticular formation important in cardiovascular control. We have termed this region, which contains C1 adrenaline‐synthesizing neurons, nucleus reticularis rostroventrolateralis (RVL). Efferent from RVL innervate all segmental levels thoracic intermediolateral intermediomedial columns as shown using retrograde...
It is widely accepted that the familial Parkinson's disease (PD)-linked gene product, parkin, functions as a ubiquitin ligase involved in protein turnover via ubiquitin-proteasome system. Substrates ubiquitinated by parkin are hence thought to be destined for proteasomal degradation. Because we demonstrated previously interacts with and ubiquitinates synphilin-1, initially expected synphilin-1 degradation enhanced presence of parkin. Contrary our expectation, found normally nonclassical,...
Huntington's Disease (HD) is caused by expansion of a CAG repeat within putative open reading frame recently identified gene, IT15. We have examined the expression gene's protein product using antibodies developed against N-terminus and an internal epitope. Both antisera recognize 350 kDa protein, predicted size, indicating that translated into polyglutamine. The HD widely expressed, most highly in neurons brain. There no enrichment striatum, site greatest pathology HD. Within neurons,...
Abstract Projections from the nucleus tractus solitarii (NTS) to autonomic control regions of ventrolateral medulla, particularly reticularis rostroventrolateralis (RVL), which serves as a tonic vasomotor center, were analyzed in rat by anterograde, retrograde, and combined axonal transport techniques. Autonomic portions NTS, including its commissural, dorsal, intermediate, interstitial, ventral, subnuclei directly project RVL well other medulla. The projections are organized...
We have explored the cellular loci of endothelin (ET) actions and formation in brain, using cerebellar mutant mice as well primary continuous cell cultures. A glial role is favored by several observations: (i) lacking neuronal Purkinje cells display normal ET receptor binding enhanced stimulation inositolphospholipid turnover; (ii) weaver granule cells, turnover not significantly diminished; (iii) C6 glioma cultures astroglia exhibit substantial ET-induced (iv) promotes mitogenesis...