Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Parkinson Disease: HELP
Articles from Nebraska
Based on 57 articles published since 2008

These are the 57 published articles about Parkinson Disease that originated from Nebraska during 2008-2019.
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Review Triggers, Facilitators, and Aggravators: Redefining Parkinson's Disease Pathogenesis. 2019

Johnson, Michaela E / Stecher, Benjamin / Labrie, Viviane / Brundin, Lena / Brundin, Patrik. ·Center for Neurodegenerative Science, Van Andel Research Institute, 333 Bostwick Avenue, NE, Grand Rapids, MI 49503, USA; These authors contributed equally to this work. · Tomorrow Edition, Toronto, Canada; These authors contributed equally to this work. · Center for Neurodegenerative Science, Van Andel Research Institute, 333 Bostwick Avenue, NE, Grand Rapids, MI 49503, USA. · Center for Neurodegenerative Science, Van Andel Research Institute, 333 Bostwick Avenue, NE, Grand Rapids, MI 49503, USA. Electronic address: Patrik.Brundin@vai.org. ·Trends Neurosci · Pubmed #30342839.

ABSTRACT: We hypothesize that Parkinson's disease (PD) pathogenesis can be divided into three temporal phases. During the first phase, 'triggers', such as viral infections or environmental toxins, spark the disease process in the brain and/or peripheral tissues. Triggers alone, however, may be insufficient, requiring 'facilitators' like peripheral inflammation for PD pathology to develop. Once the disease manifests, 'aggravators' spur further neurodegeneration and exacerbate symptoms. Aggravators are proposed to include impaired autophagy and cell-to-cell propagation of α-synuclein pathology. We believe clinical trials need to consider these three phases and target potential therapies at the appropriate stage of the disease process in order to be effective.

2 Review Neuroprotection through flavonoid: Enhancement of the glyoxalase pathway. 2018

Frandsen, Joel R / Narayanasamy, Prabagaran. ·Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5900, USA. · Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5900, USA. Electronic address: p.narayanasamy@unmc.edu. ·Redox Biol · Pubmed #29080525.

ABSTRACT: The glyoxalase pathway functions to detoxify reactive dicarbonyl compounds, most importantly methylglyoxal. The glyoxalase pathway is an antioxidant defense mechanism that is essential for neuroprotection. Excessive concentrations of methylglyoxal have deleterious effects on cells, leading to increased levels of inflammation and oxidative stress. Neurodegenerative diseases - including Alzheimer's, Parkinson's, Aging and Autism Spectrum Disorder - are often induced or exacerbated by accumulation of methylglyoxal. Antioxidant compounds possess several distinct mechanisms that enhance the glyoxalase pathway and function as neuroprotectants. Flavonoids are well-researched secondary plant metabolites that appear to be effective in reducing levels of oxidative stress and inflammation in neural cells. Novel flavonoids could be designed, synthesized and tested to protect against neurodegenerative diseases through regulating the glyoxalase pathway.

3 Review Return of D 2017

Lindsley, Craig W / Hopkins, Corey R. ·Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center , Omaha, Nebraska 68198-6125, United States. ·J Med Chem · Pubmed #28489950.

ABSTRACT: The dopamine D

4 Review Critical depurinating DNA adducts: Estrogen adducts in the etiology and prevention of cancer and dopamine adducts in the etiology and prevention of Parkinson's disease. 2017

Cavalieri, Ercole L / Rogan, Eleanor G / Zahid, Muhammad. ·Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE. · Department of Environmental, Agricultural and Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE. ·Int J Cancer · Pubmed #28388839.

ABSTRACT: Endogenous estrogens become carcinogens when dangerous metabolites, the catechol estrogen quinones, are formed. In particular, the catechol estrogen-3,4-quinones can react with DNA to produce an excess of specific depurinating estrogen-DNA adducts. Loss of these adducts leaves apurinic sites in the DNA, generating subsequent cancer-initiating mutations. Unbalanced estrogen metabolism yields excessive catechol estrogen-3,4-quinones, increasing formation of depurinating estrogen-DNA adducts and the risk of initiating cancer. Evidence for this mechanism of cancer initiation comes from various types of studies. High levels of depurinating estrogen-DNA adducts have been observed in women with breast, ovarian or thyroid cancer, as well as in men with prostate cancer or non-Hodgkin lymphoma. Observation of high levels of depurinating estrogen-DNA adducts in high risk women before the presence of breast cancer indicates that adduct formation is a critical factor in breast cancer initiation. Formation of analogous depurinating dopamine-DNA adducts is hypothesized to initiate Parkinson's disease by affecting dopaminergic neurons. Two dietary supplements, N-acetylcysteine and resveratrol complement each other in reducing formation of catechol estrogen-3,4-quinones and inhibiting formation of estrogen-DNA adducts in cultured human and mouse breast epithelial cells. They also inhibit malignant transformation of these cells. In addition, formation of adducts was reduced in women who followed a Healthy Breast Protocol that includes N-acetylcysteine and resveratrol. When initiation of cancer is blocked, promotion, progression and development of the disease cannot occur. These results suggest that reducing formation of depurinating estrogen-DNA adducts can reduce the risk of developing a variety of types of human cancer.

5 Review Metabolic Dysfunction in Parkinson's Disease: Bioenergetics, Redox Homeostasis and Central Carbon Metabolism. 2017

Anandhan, Annadurai / Jacome, Maria S / Lei, Shulei / Hernandez-Franco, Pablo / Pappa, Aglaia / Panayiotidis, Mihalis I / Powers, Robert / Franco, Rodrigo. ·School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68516, United States; Redox Biology Center, University of Nebraska-Lincoln, Lincoln, NE 68503, United States. · School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68516, United States. · Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68503, United States. · Department of Molecular Biology and Genetics, Democritus University of Thrace, University Campus, Dragana, 68100 Alexandroupolis, Greece. · School of Life Sciences, Heriot-Watt University, Edinburgh EH14 4AS, Scotland, UK. · Redox Biology Center, University of Nebraska-Lincoln, Lincoln, NE 68503, United States; Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68503, United States. · School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68516, United States; Redox Biology Center, University of Nebraska-Lincoln, Lincoln, NE 68503, United States. Electronic address: rfrancocruz2@unl.edu. ·Brain Res Bull · Pubmed #28341600.

ABSTRACT: The loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of protein inclusions (Lewy bodies) are the pathological hallmarks of Parkinson's disease (PD). PD is triggered by genetic alterations, environmental/occupational exposures and aging. However, the exact molecular mechanisms linking these PD risk factors to neuronal dysfunction are still unclear. Alterations in redox homeostasis and bioenergetics (energy failure) are thought to be central components of neurodegeneration that contribute to the impairment of important homeostatic processes in dopaminergic cells such as protein quality control mechanisms, neurotransmitter release/metabolism, axonal transport of vesicles and cell survival. Importantly, both bioenergetics and redox homeostasis are coupled to neuro-glial central carbon metabolism. We and others have recently established a link between the alterations in central carbon metabolism induced by PD risk factors, redox homeostasis and bioenergetics and their contribution to the survival/death of dopaminergic cells. In this review, we focus on the link between metabolic dysfunction, energy failure and redox imbalance in PD, making an emphasis in the contribution of central carbon (glucose) metabolism. The evidence summarized here strongly supports the consideration of PD as a disorder of cell metabolism.

6 Review Manganese-Enhanced Magnetic Resonance Imaging for Detection of Vasoactive Intestinal Peptide Receptor 2 Agonist Therapy in a Model of Parkinson's Disease. 2016

Olson, Katherine E / Bade, Aditya N / Schutt, Charles R / Dong, Jingdong / Shandler, Scott J / Boska, Michael D / Mosley, R Lee / Gendelman, Howard E / Liu, Yutong. ·Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA. · Department of Radiology, University of Nebraska Medical Center, Omaha, NE, USA. · Longevity Biotech, Philadelphia, PA, USA. · Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA. hegendel@unmc.edu. ·Neurotherapeutics · Pubmed #27329163.

ABSTRACT: Neuroprotective immunity is defined by transformation of T-cell polarity for therapeutic gain. For neurodegenerative disorders and specifically for Parkinson's disease (PD), granulocyte-macrophage colony stimulating factor or vasoactive intestinal peptide receptor 2 (VIPR2) agonists elicit robust anti-inflammatory microglial responses leading to neuronal sparing in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice. While neurotherapeutic potential was demonstrated for PD, there remain inherent limitations in translating these inventions from the laboratory to patients. One obstacle in translating such novel neurotherapeutics centers on the availability of suitable noninvasive methods to track disease progression and therapeutic efficacy. To this end, we developed manganese-enhanced magnetic resonance imaging (MEMRI) assays as a way to track a linkage between glial activation and VIPR2 agonist (LBT-3627)-induced neuroprotective immunity for MPTP-induced nigrostriatal degeneration. Notably, LBT-3627-treated, MPTP-intoxicated mice show reduced MEMRI brain signal intensities. These changes paralleled reduced astrogliosis and resulted in sparing of nigral tyrosine hydroxylase neurons. Most importantly, the data suggest that MEMRI can be developed as a biomarker tool to monitor neurotherapeutic responses that are relevant to common neurodegenerative disorders used to improve disease outcomes.

7 Review Immunomodulation as a neuroprotective and therapeutic strategy for Parkinson's disease. 2016

Olson, Katherine E / Gendelman, Howard E. ·Department of Pharmacology and Experimental Neuroscience, Center for Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 68198, USA. · Department of Pharmacology and Experimental Neuroscience, Center for Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address: hegendel@unmc.edu. ·Curr Opin Pharmacol · Pubmed #26571205.

ABSTRACT: While immune control is associated with nigrostriatal neuroprotection for Parkinson's disease, direct cause and effect relationships have not yet been realized, and modulating the immune system for therapeutic gain has been openly debated. Here, we review how innate and adaptive immunity affect disease pathobiology, and how each could be harnessed for treatment. The overarching idea is to employ immunopharmacologics as neuroprotective strategies for disease. The aim of the current work is to review disease-modifying treatments that are currently being developed as neuroprotective strategies for PD in experimental animal models and for human disease translation. The long-term goal of this research is to effectively harness the immune system to slow or prevent PD pathobiology.

8 Review A Perspective on Roles Played by Innate and Adaptive Immunity in the Pathobiology of Neurodegenerative Disorders. 2015

Gendelman, Howard E / Mosley, R Lee. ·Center for Neurodegenerative Disorders, University of Nebraska Medical Center, Department of Pharmacology and Experimental Neuroscience, Omaha, NE, 68198-5880, USA. hegendel@unmc.edu. · Center for Neurodegenerative Disorders, University of Nebraska Medical Center, Department of Pharmacology and Experimental Neuroscience, Omaha, NE, 68198-5880, USA. ·J Neuroimmune Pharmacol · Pubmed #26520433.

ABSTRACT: Aberrant innate and adaptive immune responses are neurodegenerative disease effectors. Disease is heralded by a generalized, but subtle immune activation orchestrated by the release of extracellular prion-like aggregated and oxidized or otherwise modified proteins. These are responsible for an inflammatory neurotoxic cascade. The perpetrators of such events include effector T cells and activated microglia. What ensues are Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis and stroke with changed frequencies of effector T cell and reduced numbers or function of regulatory lymphocytes. The control of such immune responses could lead to new therapeutic strategies and the means to effectively combat a composite of diseases that have quite limited therapeutic options.

9 Review Safety overview of FDA-approved medications for the treatment of the motor symptoms of Parkinson's disease. 2014

Faulkner, Michele A. ·Creighton University School of Pharmacy and Health Professions and School of Medicine , 2500 California Plaza, Omaha, NE 68178 , USA +1 402 280 3145 ; faulkner@creighton.edu. ·Expert Opin Drug Saf · Pubmed #24962891.

ABSTRACT: INTRODUCTION: Parkinson's disease (PD) is among the most common of the neurodegenerative disorders. Treatment is primarily focused on correcting neurotransmitter imbalances. Several classes of medication are available for this purpose. AREAS COVERED: A Medline search was performed to gather information about the safety of the medications approved for the treatment of the motor symptoms of PD. This was supplemented with additional articles obtained from online sources and information provided by the FDA and the manufacturers. The focus of this review is the side-effect and safety profiles of carbidopa/levodopa, dopamine agonists, selective monoamine oxidase inhibitors, catechol-o-methyltransferase inhibitors, anticholinergics and amantadine. EXPERT OPINION: Though serious side-effects may occur, as a group, the medications used for the treatment of PD motor symptoms tend to produce side-effects that are mild to moderate in nature, and that primarily reflect the focus on dopaminergic therapies. Care plans for Parkinson's patients should be approached based on the needs of the individual as disease presentation, lifestyle, level of disability, concurrent disease states and the presence of non-motor symptoms make each case unique. Patients and caregivers must have realistic expectations about the use of PD medications.

10 Review Early treatment of Parkinson's disease: opportunities for managed care. 2012

Murman, Daniel L. ·Behavioral and Geriatric Neurology Program, Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE, USA. dlmurman@ unmc.edu ·Am J Manag Care · Pubmed #23039867.

ABSTRACT: The diagnosis and treatment of Parkinson's disease (PD) typically occur when the disease has already progressed to a relatively advanced stage in which motor symptoms are clearly evident and substantial neurophysiological damage has already taken place. Nonmotor symptoms, which account for a large proportion of PD symptoms, usually emerge much earlier and offer both an early indication for treatment and a therapeutic target. A growing body of data from the medical literature points to several critical advantages that may be associated with early therapeutic intervention in PD. The most evident benefit of early intervention is a reduction in symptoms, particularly dyskinesia, and the delay of levodopa initiation. Clinical trials suggest but have yet to conclusively demonstrate that early treatment can slow disease progression. Both the diminishment of symptoms and the potential for slowing disease progression have large implications for improving patient quality of life. The enormous direct costs associated with PD would also likely be reduced over the long term with earlier treatment. The great majority of costs attributable to PD occur when the disease is at its most advanced stage and when symptoms are most severe. An early-treatment strategy that diminishes symptoms and that has the potential to slow disease progression could have a meaningful impact on PD expenditures. Adherence, too, must be taken into consideration, particularly since PD patients are generally poorly adherent to prescribed therapies, especially therapies with complex dosing schedules. Taking advantage of more convenient and adherencefriendly drug formulations may further help to improve outcomes and lower costs in PD.

11 Review Thiol-redox signaling, dopaminergic cell death, and Parkinson's disease. 2012

Garcia-Garcia, Aracely / Zavala-Flores, Laura / Rodriguez-Rocha, Humberto / Franco, Rodrigo. ·Redox Biology Center and School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA. ·Antioxid Redox Signal · Pubmed #22369136.

ABSTRACT: SIGNIFICANCE: Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta, which has been widely associated with oxidative stress. However, the mechanisms by which redox signaling regulates cell death progression remain elusive. RECENT ADVANCES: Early studies demonstrated that depletion of glutathione (GSH), the most abundant low-molecular-weight thiol and major antioxidant defense in cells, is one of the earliest biochemical events associated with PD, prompting researchers to determine the role of oxidative stress in dopaminergic cell death. Since then, the concept of oxidative stress has evolved into redox signaling, and its complexity is highlighted by the discovery of a variety of thiol-based redox-dependent processes regulating not only oxidative damage, but also the activation of a myriad of signaling/enzymatic mechanisms. CRITICAL ISSUES: GSH and GSH-based antioxidant systems are important regulators of neurodegeneration associated with PD. In addition, thiol-based redox systems, such as peroxiredoxins, thioredoxins, metallothioneins, methionine sulfoxide reductases, transcription factors, as well as oxidative modifications in protein thiols (cysteines), including cysteine hydroxylation, glutathionylation, and nitrosylation, have been demonstrated to regulate dopaminergic cell loss. FUTURE DIRECTIONS: In this review, we summarize major advances in the understanding of the role of thiol-redox signaling in dopaminergic cell death in experimental PD. Future research is still required to clearly understand how integrated thiol-redox signaling regulates the activation of the cell death machinery, and the knowledge generated should open new avenues for the design of novel therapeutic approaches against PD.

12 Review Inflammation and adaptive immunity in Parkinson's disease. 2012

Mosley, R Lee / Hutter-Saunders, Jessica A / Stone, David K / Gendelman, Howard E. ·Movement Disorders Program, Department of Pharmacology and Experimental Neuroscience, Center for Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA. ·Cold Spring Harb Perspect Med · Pubmed #22315722.

ABSTRACT: The immune system is designed to protect the host from infection and injury. However, when an adaptive immune response continues unchecked in the brain, the proinflammatory innate microglial response leads to the accumulation of neurotoxins and eventual neurodegeneration. What drives such responses are misfolded and nitrated proteins. Indeed, the antigen in Parkinson's disease (PD) is an aberrant self-protein, although the adaptive immune responses are remarkably similar in a range of diseases. Ingress of lymphocytes and chronic activation of glial cells directly affect neurodegeneration. With this understanding, new therapies aimed at modulating the immune system's response during PD could lead to decreased neuronal loss and improved clinical outcomes for disease.

13 Review Progression of motor symptoms in Parkinson's disease. 2012

Xia, Ruiping / Mao, Zhi-Hong. ·Department of Physical Therapy, School of Pharmacy and Health Professions, Creighton University, Omaha, Nebraska, USA. ruipingxia@creighton.edu ·Neurosci Bull · Pubmed #22233888.

ABSTRACT: Parkinson's disease (PD) is a chronic progressive neurodegenerative disease that is clinically manifested by a triad of cardinal motor symptoms - rigidity, bradykinesia and tremor - due to loss of dopaminergic neurons. The motor symptoms of PD become progressively worse as the disease advances. PD is also a heterogeneous disease since rigidity and bradykinesia are the major complaints in some patients whereas tremor is predominant in others. In recent years, many studies have investigated the progression of the hallmark symptoms over time, and the cardinal motor symptoms have different rates of progression, with the disease usually progressing faster in patients with rigidity and bradykinesia than in those with predominant tremor. The current treatment regime of dopamine-replacement therapy improves motor symptoms and alleviates disability. Increasing the dosage of dopaminergic medication is commonly used to combat the worsening symptoms. However, the drug-induced involuntary body movements and motor complications can significantly contribute to overall disability. Further, none of the currently-available therapies can slow or halt the disease progression. Significant research efforts have been directed towards developing neuroprotective or disease-modifying agents that are intended to slow the progression. In this article, the most recent clinical studies investigating disease progression and current progress on the development of disease-modifying drug trials are reviewed.

14 Review Immunization strategies for Parkinson's disease. 2012

Ha, Duy / Stone, David K / Mosley, R Lee / Gendelman, Howard E. ·Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA. ·Parkinsonism Relat Disord · Pubmed #22166440.

ABSTRACT: Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Currently, no curative treatments or treatments that interdict disease progression are available. Over the past decade, immunization strategies were developed in our laboratories to combat disease progression. These strategies were developed in laboratory and animal models of human disease. Induction of humoral immune responses can be elicited against misfolded protein aggregates. Robust cell-mediated immunity against nitrated misfolded protein(s) accelerates disease progression through effector T cell responses that facilitate neuronal death. We propose that shifting the balance between effector and regulatory T cell activity can attenuate neurotoxic inflammatory events. We now summarize our works that support immune regulation in PD with the singular goal of restoring homeostatic glial responses. New methods to optimize immunization schemes and measure their clinical efficacy are discussed.

15 Review Deep brain stimulation of globus pallidus interna, subthalamic nucleus, and pedunculopontine nucleus for Parkinson's disease: which target? 2012

Follett, Kenneth A / Torres-Russotto, Diego. ·Division of Neurosurgery, University of Nebraska Medical Center, Omaha, NE 68198, USA. kfollett@unmc.edu ·Parkinsonism Relat Disord · Pubmed #22166422.

ABSTRACT: Deep brain stimulation (DBS) is an accepted therapy for people with Parkinson's disease (PD) motor symptoms that are refractory to pharmacologic therapy. Standard DBS targets are globus pallidus interna (GPi) and subthalamic nucleus (STN). The pedunculopontine nucleus (PPN) is being investigated as a novel target. Which target provides the best outcomes is unknown. The utility of GPi and STN as targets has been confirmed in numerous studies, including randomized comparisons of GPi DBS and STN DBS that demonstrated no difference in motor outcomes. DBS at either site improves appendicular motor symptoms, but beneficial effects on axial manifestations of PD such as postural instability or gait dysfunction (PIGD) are less apparent. PPN has been introduced as a DBS target due to failure of GPi and STN DBS to improve PIGD. Small observational studies indicate improved PIGD with PPN DBS, but small blinded trials show only subjective reduction in falls with no other impact on PIGD or other PD manifestations. No single DBS target is superior to the others. Each target offers relative advantages. Further studies are needed to better define the roles of each target, particularly PPN. Choice of target should be individualized according to providers' preferences and patients' needs.

16 Review Pathways towards an effective immunotherapy for Parkinson's disease. 2011

Hutter-Saunders, Jessica A L / Mosley, Rodney Lee / Gendelman, Howard E. ·Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA. ·Expert Rev Neurother · Pubmed #22091596.

ABSTRACT: Immunizations that target specific types of immune responses are used commonly to prevent microbial infections. However, a range of immune responses may prove necessary to combat the ravages of neurodegenerative diseases. The goal is to eliminate the 'root' cause of neurodegenerative disorders, misfolded aggregated proteins, while harnessing adaptive immune responses to promote neural repair. However, immunization strategies used to elicit humoral immune responses against aberrant brain proteins have yielded mixed success. While specific proteins can be cleared, the failures in halting disease progression revolve, in measure, around adaptive immune responses that promote autoreactive T cells and, as such, induce a meningoencephalitis, accelerating neurodegeneration. Thus, alternative approaches for protein clearance and neural repair are desired. To this end, our laboratories have sought to transform autoreactive adaptive immune responses into regulatory neuroprotective cells in Parkinson's disease. In this context, induction of immune responses against modified brain proteins serves to break immunological tolerance, while eliciting adaptive immunity to facilitate neuronal repair. How to harness the immune response in the setting of Parkinson's disease requires a thorough understanding of the role of immunity in human disease and the ways to modify such immune responses to elicit therapeutic gain. These are discussed in this review.

17 Review Innate and adaptive immunity for the pathobiology of Parkinson's disease. 2009

Stone, David K / Reynolds, Ashley D / Mosley, R Lee / Gendelman, Howard E. ·Center for Neurovirology and Neurodegenerative Disorders, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska 68198-5880, USA. ·Antioxid Redox Signal · Pubmed #19243239.

ABSTRACT: Innate and adaptive immunity affect the pathogenesis of Parkinson's disease (PD). In particular, activation of microglia influences degeneration of dopaminergic neurons. Cell-to-cell interactions and immune regulation critical for neuronal homeostasis also influence immune responses. The links between T cell immunity and nigrostriatal degeneration are supported by laboratory, animal model, and human pathologic investigations. Immune-associated biomarkers in spinal fluids and brain tissue of patients with idiopathic or familial forms of PD provide means to improve diagnosis and therapeutic monitoring. Relationships between oxidative stress, inflammation, and immune-mediated cell death pathways are examined in this review as they are linked to PD pathogenesis. Harnessing the immune system by drugs or by vaccination remain promising future therapeutic options.

18 Article Movement Disorders and Deep Brain Stimulation in the Middle East. 2018

Siddiqui, Junaid H / Bhatti, Danish / Alsubaie, Fahd / Bajwa, Jawad A. ·University of Missouri, Columbia, Missouri, USA. · Nebraska Medical Center, University of Nebraska, Omaha, Nebraska, USA. · Department of Neurosurgery, National Neuroscience Institute, King Fahad Medical City, Riyadh, Saudi Arabia. · Parkinson's, Movement Disorders and Neurorestoration Program, National Neuroscience Institute, King Fahad Medical City, Riyadh, Saudi Arabia. Electronic address: drbajwa@gmail.com. ·World Neurosurg · Pubmed #29452314.

ABSTRACT: BACKGROUND: Deep brain stimulation (DBS) is a well-established neuromodulation therapy for advanced Parkinson disease, essential tremor and dystonia. In as much as this therapy is being developed in the Middle East, a better understanding of the incidence and prevalence of movement disorders, health care, and social framework is required for the region. METHODS: We reviewed current literature on the incidence and prevalence of various movement disorders in the Middle East amenable to DBS surgery. We also assessed recent efforts to develop DBS in the region. RESULTS: Available data on incidence and prevalence of movement disorders in the Middle East are old, inconclusive, and conflicting. We identify key areas such as cultural background, availability of accessible information, training, infrastructure, and public support groups in the region that may pose challenges. CONCLUSIONS: The Middle East is projected to be a growing market for neuromodulation. The available data on incidence and prevalence of movement disorders is from studies that were small, partial, and old, with inconsistent results, highlighting the need for newer, better-designed, and larger studies. DBS in the Middle East will need assessment of incidence and prevalence of movement disorders, existing challenges to its application, and focused efforts on key opportunities to foster development of DBS for this underserved region. This article is an attempt to identify and explore these challenges and propose solutions in anticipation.

19 Article Survival in patients with Parkinson's disease after deep brain stimulation or medical management. 2017

Weaver, Frances M / Stroupe, Kevin T / Smith, Bridget / Gonzalez, Beverly / Huo, Zhiping / Cao, Lishan / Ippolito, Dolores / Follett, Kenneth A. ·Hines Veterans Affairs Hospital, Center of Innovation for Complex Chronic Healthcare, Hines, Illinois, USA. · Loyola University Stritch School of Medicine, Maywood, Illinois, USA. · Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. · University of Nebraska School of Medicine, Omaha, Nebraska, USA. ·Mov Disord · Pubmed #29150873.

ABSTRACT: OBJECTIVE: Deep brain stimulation has been shown to have a significant long-term beneficial effect on motor function. However, whether it affects survival is not clear. In this study, we compared survival rates for Parkinson's disease (PD) patients who underwent deep brain stimulation (DBS) with those who were medically managed. METHODS: A retrospective analysis of Veterans Affairs and Medicare administrative data of veterans with PD who received DBS and were propensity score matched to a cohort of veterans with PD who did not receive DBS between 2007-2013. RESULTS: Veterans with PD who received DBS had a longer survival measured in days than a matched group of veterans who did not undergo DBS (mean = 2291.1 [standard error = 46.4] days [6.3 years] vs 2063.8 [standard error = 47.7] days [5.7 years]; P = .006; hazard ratio = 0.69 [95% confidence interval 0.56-0.85]). Mean age at death was similar for both groups (76.5 [standard deviation = 7.2] vs 75.9 [standard deviation = 8.4] years, P = .67), respectively, and the most common cause of death was PD. CONCLUSIONS: DBS is associated with a modest survival advantage when compared with a matched group of patients who did not undergo DBS. Whether the survival advantage reflects a moderating influence of DBS on PD or on comorbidities that might shorten life or whether differences may be a result of unmeasured differences between groups is not known. © 2017 International Parkinson and Movement Disorder Society.

20 Article Structural Biology of the DJ-1 Superfamily. 2017

Smith, Nathan / Wilson, Mark A. ·Department of Biochemistry and the Redox Biology Center, University of Nebraska, Lincoln, NE, 68588, USA. · Department of Biochemistry and the Redox Biology Center, University of Nebraska, Lincoln, NE, 68588, USA. mwilson13@unl.edu. ·Adv Exp Med Biol · Pubmed #29147900.

ABSTRACT: The DJ-1 (also called the DJ-1/PfpI, ThiJ/PfpI, or DJ-1/ThiJ/PfpI) superfamily is a structural and functional diverse group of proteins that are present in most organisms. Many of these proteins remain poorly characterized at the biochemical level, but include some known chaperones, proteases, and various stress response proteins that remain mechanistically mysterious. This chapter outlines what is known from a structural perspective about the cellular and biochemical functions of many of these proteins from distinct clades of the superfamily in several organisms. In humans, DJ-1 appears to function primarily as a redox-responsive protein that may act as a sensor for imbalances in cellular redox state. Because mutations in human DJ-1 cause certain types of heritable Parkinson's disease, the role of oxidative posttranslational modifications and pathogenic mutations in human DJ-1 is emphasized in the latter sections of this chapter.

21 Article Longitudinal decline of driving safety in Parkinson disease. 2017

Uc, Ergun Y / Rizzo, Matthew / O'Shea, Amy M J / Anderson, Steven W / Dawson, Jeffrey D. ·From the Departments of Neurology (E.Y.U., M.R., S.W.A.) and Biostatistics (A.M.J.O., J.D.D.), University of Iowa · Neurology Service (E.Y.U.) and Comprehensive Access and Delivery Research & Evaluation (A.M.J.O.), Veterans Affairs Medical Center, Iowa City, IA · and Department of Neurology (M.R.), University of Nebraska, Omaha. ·Neurology · Pubmed #29021353.

ABSTRACT: OBJECTIVE: To longitudinally assess and predict on-road driving safety in Parkinson disease (PD). METHODS: Drivers with PD (n = 67) and healthy controls (n = 110) drove a standardized route in an instrumented vehicle and were invited to return 2 years later. A professional driving expert reviewed drive data and videos to score safety errors. RESULTS: At baseline, drivers with PD performed worse on visual, cognitive, and motor tests, and committed more road safety errors compared to controls (median PD 38.0 vs controls 30.5; CONCLUSIONS: Despite drop out of the more impaired drivers within the PD cohort, returning drivers with PD, who drove like controls without PD at baseline, showed many more driving safety errors than controls after 2 years. Driving decline in PD was predicted by baseline driving performance and deterioration of cognitive, visual, and functional abnormalities on follow-up.

22 Article Utilization of rehabilitation therapy services in Parkinson disease in the United States. 2017

Fullard, Michelle E / Thibault, Dylan P / Hill, Andrew / Fox, Joellyn / Bhatti, Danish E / Burack, Michelle A / Dahodwala, Nabila / Haberfeld, Elizabeth / Kern, Drew S / Klepitskava, Olga S / Urrea-Mendoza, Enrique / Myers, Phillip / Nutt, Jay / Rafferty, Miriam R / Schwalb, Jason M / Shulman, Lisa M / Willis, Allison W / Anonymous1580917. ·From the Departments of Neurology (M.E.F., D.P.T., A.H., N.D., A.W.W.) and Biostatistics and Epidemiology (D.P.T., A.H., A.W.W.), University of Pennsylvania School of Medicine · Dan Aaron Parkinson's Rehabilitation Center (J.F.), Leonard Davis Institute of Health Economics (A.W.W.), and Center for Clinical Epidemiology and Biostatistics (A.W.W.), University of Pennsylvania, Philadelphia · Department of Neurobiological Sciences (D.E.B.), University of Nebraska Medical Center, Omaha · Department of Neurology (M.A.B.), University of Rochester, NY · Department of Neurology (E.H.), Temple University, Philadelphia, PA · Department of Neurology (D.S.K., O.S.K.), University of Colorado, Aurora · Greenville Health System (E.-U.M.), SC · Parkinson's Disease Foundation Advocate Group (P.M.), Lakeport, CA · Department of Neurology (J.N.), Oregon Health Sciences University, Portland · Center for Education in Health Sciences (M.R.R.), Northwestern University, Evanston, IL · Department of Neurosurgery (J.M.S.), Henry Ford Medical Group, Detroit, MI · Department of Neurology (L.M.S.), University of Maryland School of Medicine, Baltimore. ·Neurology · Pubmed #28835397.

ABSTRACT: OBJECTIVE: To examine rehabilitation therapy utilization for Parkinson disease (PD). METHODS: We identified 174,643 Medicare beneficiaries with a diagnosis of PD in 2007 and followed them through 2009. The main outcome measures were annual receipt of physical therapy (PT), occupational therapy (OT), or speech therapy (ST). RESULTS: Outpatient rehabilitation fee-for-service use was low. In 2007, only 14.2% of individuals with PD had claims for PT or OT, and 14.6% for ST. Asian Americans were the highest users of PT/OT (18.4%) and ST (18.4%), followed by Caucasians (PT/OT 14.4%, ST 14.8%). African Americans had the lowest utilization (PT/OT 7.8%, ST 8.2%). Using logistic regression models that accounted for repeated measures, we found that African American patients (adjusted odds ratio [AOR] 0.63 for PT/OT, AOR 0.63 for ST) and Hispanic patients (AOR 0.97 for PT/OT, AOR 0.91 for ST) were less likely to have received therapies compared to Caucasian patients. Patients with PD with at least one neurologist visit per year were 43% more likely to have a claim for PT evaluation as compared to patients without neurologist care (AOR 1.43, 1.30-1.48), and this relationship was similar for OT evaluation, PT/OT treatment, and ST. Geographically, Western states had the greatest use of rehabilitation therapies, but provider supply did not correlate with utilization. CONCLUSIONS: This claims-based analysis suggests that rehabilitation therapy utilization among older patients with PD in the United States is lower than reported for countries with comparable health care infrastructure. Neurologist care is associated with rehabilitation therapy use; provider supply is not.

23 Article Polar-phase indices of perioral muscle reciprocity during syllable production in Parkinson's disease. 2017

Chu, Shin Ying / Barlow, Steven M / Lee, Jaehoon / Wang, Jingyan. ·a Faculty of Health Sciences, Speech Sciences Programme , Universiti Kebangsaan Malaysia , Kuala Lumpur , Malaysia. · b Department of Special Education and Communication Disorders, Biological Systems Engineering, Center for Brain, Biology and Behavior , Communication Neuroscience Laboratories, University of Nebraska , Lincoln , NE , USA. · c College of Education , Institute for Measurement, Methodology, Analysis and Policy (IMMAP), Texas Tech University , Lubbock , TX , USA , and. · d Communication Neuroscience Laboratories , University of Nebraska , Lincoln , NE , USA. ·Int J Speech Lang Pathol · Pubmed #28425760.

ABSTRACT: PURPOSE: This research characterised perioral muscle reciprocity and amplitude ratio in lower lip during bilabial syllable production [pa] at three rates to understand the neuromotor dynamics and scaling of motor speech patterns in individuals with Parkinson's disease (PD). METHOD: Electromyographic (EMG) signals of the orbicularis oris superior [OOS], orbicularis oris inferior [OOI] and depressor labii inferioris [DLI] were recorded during syllable production and expressed as polar-phase notations. RESULT: PD participants exhibited the general features of reciprocity between OOS, OOI and DLI muscles as reflected in the EMG during syllable production. The control group showed significantly higher integrated EMG amplitude ratio in the DLI:OOS muscle pairs than PD participants. No speech rate effects were found in EMG muscle reciprocity and amplitude magnitude across all muscle pairs. CONCLUSION: Similar patterns of muscle reciprocity in PD and controls suggest that corticomotoneuronal output to the facial nucleus and respective perioral muscles is relatively well-preserved in our cohort of mild idiopathic PD participants. Reduction of EMG amplitude ratio among PD participants is consistent with the putative reduction in the thalamocortical activation characteristic of this disease which limits motor cortex drive from generating appropriate commands which contributes to bradykinesia and hypokinesia of the orofacial mechanism.

24 Article The cortical signature of symptom laterality in Parkinson's disease. 2017

Heinrichs-Graham, Elizabeth / Santamaria, Pamela M / Gendelman, Howard E / Wilson, Tony W. ·Department of Neurological Sciences, University of Nebraska Medical Center (UNMC), Omaha, NE, USA; Center for Magnetoencephalography, UNMC, Omaha, NE, USA. · Department of Neurology, Neurology Consultants of Nebraska, Omaha, NE, USA. · Department of Pharmacology & Experimental Neuroscience, UNMC, Omaha, NE, USA. · Department of Neurological Sciences, University of Nebraska Medical Center (UNMC), Omaha, NE, USA; Center for Magnetoencephalography, UNMC, Omaha, NE, USA; Department of Pharmacology & Experimental Neuroscience, UNMC, Omaha, NE, USA. ·Neuroimage Clin · Pubmed #28271041.

ABSTRACT: Patients with Parkinson's disease (PD) often present with unilateral motor symptoms that eventually spread to the other side. This symptom lateralization is diagnostically important, as it serves to distinguish PD from other motor disorders with overlapping symptom profiles. Further, recent studies have shown that the side of symptom onset is important for prognosis, as there are differences in the rate of disease progression and the incidence of secondary symptoms between right- and left-dominant (RD, LD) patients. Physiologically, previous studies have shown asymmetrical decline in structure and metabolism throughout the basal ganglia, although connecting this directly to motor function has been difficult. To identify the neurophysiological basis of symptom laterality in PD, we recorded magnetoencephalography (MEG) during left- and right-hand movement paradigms in patients with PD who exhibited either RD or LD symptomatology. The beta oscillations serving these movements were then imaged using beamforming methods, and we extracted the time series of the peak voxel in the left and right primary motor cortices for each movement. In addition, each patient's symptom asymmetry was quantitated using the Unified Parkinson's Disease Rating Scale (UPDRS), which allowed the relationship between symptom asymmetry and neural asymmetry to be assessed. We found that LD patients had stronger beta suppression during movement, as well as greater post-movement beta rebound compared to patients with RD symptoms, independent of the hand that was moved. Interestingly, the asymmetry of beta activity during right-hand movement uniquely correlated with symptom asymmetry, such that the more LD the symptom profile, the more left-lateralized (i.e., contralateral to movement) the beta response; conversely, the more RD the symptom profile, the more right-lateralized (i.e., ipsilateral to movement) the beta response. This study is the first to directly probe the relationship between symptom asymmetry and the laterality of neural activity during movement in patients with PD, and suggests that LD patients have a fundamentally different and more "healthy" oscillatory pattern relative to RD patients.

25 Article Validation of an improved scale for rating l-DOPA-induced dyskinesia in the mouse and effects of specific dopamine receptor antagonists. 2016

Sebastianutto, Irene / Maslava, Natallia / Hopkins, Corey R / Cenci, M Angela. ·Basal Ganglia Pathophysiology Unit, Dept. Exp. Medical Science, Lund University, BMC, 221 84 Lund, Sweden. Electronic address: irene.sebastianutto@med.lu.se. · Basal Ganglia Pathophysiology Unit, Dept. Exp. Medical Science, Lund University, BMC, 221 84 Lund, Sweden. · Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198-6125, USA. · Basal Ganglia Pathophysiology Unit, Dept. Exp. Medical Science, Lund University, BMC, 221 84 Lund, Sweden. Electronic address: angela.cenci_nilsson@med.lu.se. ·Neurobiol Dis · Pubmed #27597526.

ABSTRACT: Rodent models of l-DOPA-induced dyskinesia (LID) are essential to investigate pathophysiological mechanisms and treatment options. Ratings of abnormal involuntary movements (AIMs) are used to capture both qualitative and quantitative features of dyskinetic behaviors. Thus far, validated rating scales for the mouse have anchored the definition of severity to the time during which AIMs are present. Here we have asked whether the severity of axial, limb, and orolingual AIMs can be objectively assessed with scores based on movement amplitude. Mice sustained 6-OHDA lesions in the medial forebrain bundle and were treated with l-DOPA (3-6mg/kg/day) until they developed stable AIMs scores. Two independent investigators rated AIM severity using both the validated time-based scale and a novel amplitude scale, evaluating the degree of deviation of dyskinetic body parts relative to their resting position. The amplitude scale yielded a high degree of consistency both within- and between raters. Thus, time-based scores, amplitude scores, and a combination of the two ('global AIM scores') were applied to compare antidyskinetic effects produced by amantadine and by the following subtype-specific DA receptor antagonists: SCH23390 (D1/D5), Raclopride (D2/D3), PG01037 (D3), L-745,870 (D4), and VU6004461 (D4). SCH23390 and Raclopride produced similarly robust reductions in both time-based scores and amplitude scores, while PG01037 and L-745,870 had more partial effects. Interestingly, a novel and highly brain penetrable D4 receptor antagonist (VU6004461) markedly attenuated both time-based and amplitude scores without diminishing the general motor stimulant effect of l-DOPA. In summary, our results show that a dyskinesia scale combining a time dimension with an amplitude dimension ('global AIMs') is more sensitive than unidimensional scales. Moreover, the antidyskinetic effects produced by two chemically distinct D4 antagonists identify the D4 receptor as a potential future target for the treatment of LID.