%0 Journal Article
%T Potential Benefits of Therapeutic Use of ¦Â2-Adrenergic Receptor Agonists in Neuroprotection and Parkinson¦Ìs Disease
%A Lynda Peterson
%A Kathleen P. Ismond
%A Elisha Chapman
%A Patrick Flood
%J Journal of Immunology Research
%D 2014
%R 10.1155/2014/103780
%X The ¦Â2-adrenergic receptor (¦Â2AR) is a seven-transmembrane (7TM) G-protein coupled receptor that is expressed on cells of the pulmonary, cardiac, skeletal muscle, and immune systems. Previous work has shown that stimulation of this receptor on immune cells has profound effects on the regulatory activity of both adaptive and innate immune cells. This review examines the functional dichotomy associated with stimulation of ¦Â2AR and microglial cells. As well, recent studies targeting these receptors with long-acting agonists are considered with respect to their therapeutic potential in management of Parkinson¦Ìs disease. 1. Introduction Neurodegenerative disorders, such as Alzheimer¡¯s, Huntington¡¯s, and Parkinson¡¯s disease, are characterized by the progressive loss of the structure and function of neurons. Specifically, Parkinson¡¯s disease is characterized by the death of dopaminergic (DA) neurons (cell groups A8 and A9) in the midbrain, substantia nigra (SN), and striatum. Over time, this leads to impaired motor skills, shaking, slowness of movement, and postural instability, well known symptoms of PD. In addition, many patients experience dementia and executive dysfunction. A recent study of an unselected population-representative cohort ( ) highlights the poor prognosis of PD patients as evidenced by a 55% mortality rate within 10 years of diagnosis [1]. Of the survivors, 68% and 46% had postural instability and dementia, respectively; 23% had not yet progressed to either of these irreversible disease milestones. Since the late 1960s, levodopa has been a key treatment and is the gold standard nearly 50 years later [2]. Converted to dopamine within the brain, it is used to control the motor symptoms of the disease but is ineffective with respect to dementia, freezing, or autonomic functions. A host of other treatments have been developed centered primarily around maintaining or increasing dopamine concentrations within the brain, such as dopamine agonists, MAO B inhibitors, catechol o-methyltransferase (COMT) inhibitors, anticholinergics, and amantadine. Stem cell transplant therapy and deep brain stimulation have also been explored with varying results. What is known about neurodegenerative disorders in general and in Parkinson¡¯s disease in particular is that the progressive nature is in part associated with chronic inflammation and microglial activation [3]. Although a variety of triggers, including inherited genetic mutations and environmental toxins, can initiate the advent of neurodegeneration, inflammation is now recognized as an underlying mechanism
%U http://www.hindawi.com/journals/jir/2014/103780/