A5000374325- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Neuroscience and Neuropharmacology Research
- Genetic Neurodegenerative Diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Nuclear Receptors and Signaling
- Receptor Mechanisms and Signaling
- Alzheimer's disease research and treatments
- Restless Legs Syndrome Research
- Botulinum Toxin and Related Neurological Disorders
- RNA regulation and disease
- Autism Spectrum Disorder Research
- Nerve injury and regeneration
- Cellular transport and secretion
- Dysphagia Assessment and Management
- Ion channel regulation and function
- Neurological diseases and metabolism
- Child Nutrition and Feeding Issues
- CAR-T cell therapy research
- Mitochondrial Function and Pathology
- Neurogenesis and neuroplasticity mechanisms
- Lysosomal Storage Disorders Research
- Memory and Neural Mechanisms
- T-cell and B-cell Immunology
- Parkinson's Disease and Spinal Disorders
University of Alabama at Birmingham
2016-2025
Research Network (United States)
2021-2025
Neurology, Inc
2016-2025
Van Andel Institute
2024
Georgetown University
2024
University of Rochester
2000-2024
University of Pittsburgh
2024
University of Colorado Anschutz Medical Campus
2024
University of Alabama
2014-2021
Krembil Research Institute
2019-2020
Huntington's disease (HD) is an inherited neurodegenerative caused by expansion of a polyglutamine tract in the huntingtin protein. Transcriptional dysregulation has been implicated HD pathogenesis. Here, we report that interacts with transcriptional activator Sp1 and coactivator TAFII130. Coexpression TAFII130 cultured striatal cells from wild-type transgenic mice reverses inhibition dopamine D2 receptor gene mutant huntingtin, as well protects neurons huntingtin-induced cellular toxicity....
This paper presents the results of a pilot study to assess feasibility using accelerometer data estimate severity symptoms and motor complications in patients with Parkinson's disease. A support vector machine (SVM) classifier was implemented tremor, bradykinesia dyskinesia from features. SVM-based estimates were compared clinical scores derived via visual inspection video recordings taken while performed series standardized tasks. The analysis by clinicians trained use scales for assessment...
<h3>Background</h3> The best way to initiate dopaminergic therapy for early Parkinson disease remains unclear. <h3>Objective</h3> To compare initial treatment with pramipexole vs levodopa in disease, followed by supplementation, respect the development of motor complications, other adverse events, and functional quality-of-life outcomes. <h3>Design</h3> Multicenter, parallel-group, double-blind, randomized controlled trial. <h3>Setting</h3> Academic movement disorders clinics at 22 sites...
We describe a novel mechanism for vital fluorescent dye entry into sensory cells and neurons: permeation through ion channels. In addition to the slow conventional uptake of styryl dyes by endocytosis, small such as FM1-43 rapidly specifically label hair in inner ear entering open mechanotransduction This labeling can be blocked pharmacological or mechanical closing phenomenon is not limited cell transduction channels, because human embryonic kidney 293T expressing vanilloid receptor (TRPV1)...
Metabotropic glutamate receptors (mGluRs) couple the actions of to intracellular second messenger systems through G-proteins. The mGluRs play an important role in regulation basal ganglia function. Ligand binding studies have revealed that contain at least two pharmacological types metabotropic sites. Agonists can affect both vitro electrophysiologic responses striatal neurons and motor behavior vivo. Recently, cDNAs encoding five been cloned, each with distinct structural properties. In...
Parkinson's disease (PD) progresses relentlessly and affects five million people worldwide. Laboratory tests for PD are critically needed developing treatments designed to slow or prevent progression of the disease. We performed a transcriptome-wide scan in 105 individuals interrogate molecular processes perturbed cellular blood patients with early-stage PD. The multigene marker here identified is associated risk 66 samples training set comprising healthy controls [third tertile...
Extracellular adenosine critically modulates ischemic brain injury, at least in part through activation of the A 1 receptor. However, role played by 2A receptor has been obscured intrinsic limitations adenosinergic agents. To overcome these pharmacological limitations, we explored consequences deleting on damage after transient focal ischemia. Cerebral morphology, as well vascular and physiological measures (before, during, ischemia) did not differ between knock-out wild-type littermates....
Missense mutations in leucine-rich repeat kinase 2 (LRRK2) cause late-onset Parkinson's disease (PD), and common genetic variation LRRK2 modifies susceptibility to Crohn's leprosy. High levels of expression peripheral monocytes macrophages suggest a role for these cells, yet little is known about function immune cells the brain. Here, we demonstrate mediating microglial proinflammatory responses morphology. In murine model neuroinflammation, observe robust induction microglia. Experiments...
Abstract We studied afferents to the parabrachial nucleus (PB) from spinal cord and trigeminal pars caudalis (SNVc) in rat by using anterograde retrograde transport of wheat germ agglutinin conjugated horseradish peroxidase (WGA‐HRP). Injections WGA‐HRP into medial PB retrogradely labeled neurons promontorium lamina I dorsal rostral SNVc, while injections lateral Kölliker‐Fuse these areas as well throughout caudal SNVc horn. horn resulted terminal labeling dorsal, central, external subnuclei...
Abstract Glutamate is an important neurotransmitter in the circuitry of basal ganglia. Of four pharmacological classes receptors that many mediate actions glutamate, N‐methyl‐D‐aspartate (NMDA) type particular interest insofar as it has been implicated neural processes underlying long‐term synaptic plasticity well excitotoxic injury. NMDA ligand binding sites are abundant structures ganglia, and have linked to neuronal excitability, neuropeptide gene expression, regulation dopamine release...
<h3>Importance</h3> We observed a significant correlation between cerebrospinal fluid (CSF) levels of tau proteins and α-synuclein, but not β-amyloid 1-42 (Aβ1-42), lower concentration CSF biomarkers, as compared with healthy controls, in cohort entirely untreated patients Parkinson disease (PD) at the earliest stage studied so far. <h3>Objective</h3> To evaluate baseline characteristics relationship to clinical features biomarkers (Aβ1-42, total [T-tau], phosphorylated threonine 181...
Antisera to atriopeptin III and a cyanogen bromide fragment of the precursor molecule atriopeptigen were prepared used examine distribution atriopeptin-like immunoreactive material in heart brain rat. Granules this seen myocytes throughout right left atria densest perinuclear region. The is consistent with previous reports atrial secretory granules. In neurons containing observed hypothalamus pontine tegmentum. Atriopeptin may serve as neurotransmitter neural systems controlling blood volume...
Accumulation of α-synuclein (α-syn) in the brain is a core feature Parkinson disease (PD) and leads to microglial activation, production inflammatory cytokines chemokines, T-cell infiltration, neurodegeneration. Here, we have used both an <i>in vivo</i> mouse model induced by viral overexpression α-syn as well vitro</i> systems study role MHCII complex α-syn-induced neuroinflammation We find that vivo</i>, expression full-length human causes striking induction microglia, while knock-out...
Microglial activation and adaptive immunity have been implicated in the neurodegenerative processes Parkinson disease. It has proposed that these responses may be triggered by modified forms of α-synuclein (α-SYN), particularly nitrated species, which are released as a consequence dopaminergic neurodegeneration. To examine relationship between α-SYN, microglial activation, immunity, we used mouse model disease human α-SYN is overexpressed recombinant adeno-associated virus vector, serotype 2...
Abstract A diagnosis of motor Parkinson’s disease (PD) is preceded by a prolonged premotor phase with accumulating neuronal damage. Here we examined the temporal relation between α-synuclein (α-syn) T cell reactivity and PD. longitudinal case study revealed that elevated α-syn-specific responses were detected prior to PD, declined after. The relationship early PD in two independent cohorts showed highest shortly after then decreased. Additional analysis significant association age lower...
Animal models and clinical studies have linked the innate adaptive immune system to pathology of Parkinson's disease (PD). Despite such progress, specific responses that influence progression eluded investigators. Herein, we assessed relationships between T cell phenotype function with PD progression. Peripheral blood lymphocytes from two separate cohorts, a discovery cohort validation cohort, totaling 113 patients 96 age- environment-matched caregivers were examined by flow cytometric...
Parkinson's Disease (PD) is an age-related, chronic neurodegenerative disorder. At present, there are no disease-modifying therapies to prevent PD progression. Activated microglia and neuroinflammation associated with the pathogenesis progression of PD. Accumulation α-synuclein (α-SYN) in brain a core feature leads microglial activation, inflammatory cytokine/chemokine production, ultimately neurodegeneration. Given importance JAK/STAT pathway activating inducing expression, we investigated...
Increasing evidence points to inflammation as a chief mediator of Parkinson9s disease (PD), progressive neurodegenerative disorder characterized by loss dopamine neurons in the substantia nigra pars compacta (SNpc) and widespread aggregates protein α-synuclein (α-syn). Recently, microRNAs, small, noncoding RNAs involved regulating gene expression at posttranscriptional level, have been recognized important regulators inflammatory environment. Using an array approach, we found significant...