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      Utility of Neuronal-Derived Exosomes to Examine Molecular Mechanisms That Affect Motor Function in Patients With Parkinson Disease : A Secondary Analysis of the Exenatide-PD Trial

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          Abstract

          Exenatide, a glucagon-like peptide 1 agonist used in type 2 diabetes, was recently found to have beneficial effects on motor function in a randomized, placebo-controlled trial in Parkinson disease (PD). Accumulating evidence suggests that impaired brain insulin and protein kinase B (Akt) signaling play a role in PD pathogenesis; however, exploring the extent to which drugs engage with putative mechnisms in vivo remains a challenge.

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          Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases.

          A J Hughes, S Daniel, L Kilford … (1992)
          Article 0 comments Cited 604 times – based on 0 reviews     Review now
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            Standardization of sample collection, isolation and analysis methods in extracellular vesicle research

            Kenneth W Witwer, Edit Buzás, Lynne T. Bemis … (2013)
            The emergence of publications on extracellular RNA (exRNA) and extracellular vesicles (EV) has highlighted the potential of these molecules and vehicles as biomarkers of disease and therapeutic targets. These findings have created a paradigm shift, most prominently in the field of oncology, prompting expanded interest in the field and dedication of funds for EV research. At the same time, understanding of EV subtypes, biogenesis, cargo and mechanisms of shuttling remains incomplete. The techniques that can be harnessed to address the many gaps in our current knowledge were the subject of a special workshop of the International Society for Extracellular Vesicles (ISEV) in New York City in October 2012. As part of the “ISEV Research Seminar: Analysis and Function of RNA in Extracellular Vesicles (evRNA)”, 6 round-table discussions were held to provide an evidence-based framework for isolation and analysis of EV, purification and analysis of associated RNA molecules, and molecular engineering of EV for therapeutic intervention. This article arises from the discussion of EV isolation and analysis at that meeting. The conclusions of the round table are supplemented with a review of published materials and our experience. Controversies and outstanding questions are identified that may inform future research and funding priorities. While we emphasize the need for standardization of specimen handling, appropriate normative controls, and isolation and analysis techniques to facilitate comparison of results, we also recognize that continual development and evaluation of techniques will be necessary as new knowledge is amassed. On many points, consensus has not yet been achieved and must be built through the reporting of well-controlled experiments.
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              Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson’s disease

              Seung Yun, Tae-In Kam, Nikhil Panicker … (2018)
              Activation of microglia by classical inflammatory mediators can convert astrocytes to a neurotoxic A1 phenotype in a variety of neurological diseases 1,2 . Development of agents that could inhibit the formation of A1 reactive astrocytes could be used to treat these diseases for which there are no disease modifying therapies. Glucagon-like peptide-1 receptor (GLP-1R) agonists have been touted as potential neuroprotective agents for neurologic disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) 3-13 . The mechanisms by which GLP-1R agonists are neuroprotective are not known. Here we show that a potent, brain penetrant long acting GLP-1R agonist NLY01 protects against the loss of dopamine neurons and behavioral deficits in the α-synuclein preformed fibril (α-syn PFF) model of sporadic PD 14,15 . NLY01 also prolongs the life and reduces the behavioral deficits and neuropathological abnormalities in the human A53T α-synuclein (hA53T) transgenic (Tg) model of α-synucleinopathy induced neurodegeneration 16 . We found that NLY01 is a potent GLP-1R agonist with favorable properties that is neuroprotective via the direct prevention of microglial mediated conversion of astrocytes to an A1 neurotoxic phenotype. In light of NLY01 favorable properties it should be evaluated in the treatment of PD and related neurologic disorders characterized by microglial activation.
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                Author and article information

                Journal
                Title: JAMA Neurology
                Abbreviated Title: JAMA Neurol
                Publisher: American Medical Association (AMA)
                ISSN (Print): 2168-6149
                Publication date Created: April 01 2019
                Publication date (Print): April 01 2019
                Volume: 76
                Issue: 4
                Page: 420
                Affiliations
                [1 ]Department of Clinical and Movement Neurosciences, University College London Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, United Kingdom
                [2 ]Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland
                [3 ]Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland
                [4 ]University College London Comprehensive Clinical Trials Unit, London, United Kingdom
                [5 ]School of Biosciences and Medicine, University of Surrey, Kent, United Kingdom
                Article
                DOI: 10.1001/jamaneurol.2018.4304
                PMC ID: 6459135
                PubMed ID: 30640362
                SO-VID: f1ca86c7-0b4f-4209-906f-d18be9b9af1d
                Copyright © © 2019
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