The dopamine transporter: An unrecognized nexus for dysfunctional peripheral immunity and signaling in Parkinson’s Disease
| Autor: | Emily Nickoloff, Phillip Mackie, Peter J. Gaskill, Leila Saadatpour, Habibeh Khoshbouei, Joe J Lebowitz |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Parkinson's disease Dopamine Dopamine Plasma Membrane Transport Proteins Immunology Context (language use) Monocytes Article 03 medical and health sciences Behavioral Neuroscience Humans Medicine Lymphocytes Neuroinflammation Dopamine transporter biology Endocrine and Autonomic Systems business.industry Dopaminergic Neurons Macrophages Dopaminergic Neurodegenerative Diseases Parkinson Disease medicine.disease 030104 developmental biology Neuroimmunology Nerve Degeneration alpha-Synuclein biology.protein business Neuroscience Signal Transduction medicine.drug |
| Zdroj: | Brain, Behavior, and Immunity. 70:21-35 |
| ISSN: | 0889-1591 |
| Popis: | The second-most common neurodegenerative disease, Parkinson’s Disease (PD) has three hallmarks: dysfunctional dopamine transmission due, at least in part, to dopamine neuron degeneration; intracellular inclusions of α-synuclein aggregates; and neuroinflammation. The origin and interplay of these features remains a puzzle, as does the underlying mechanism of PD pathogenesis and progression. When viewed in the context of neuroimmunology, dopamine also plays a role in regulating peripheral immune cells. Intriguingly, plasma dopamine levels are altered in PD, suggesting collateral dysregulation of peripheral dopamine transmission. The dopamine transporter (DAT), the main regulator of dopaminergic tone in the CNS, is known to exist in lymphocytes and monocytes/macrophages, but little is known about peripheral DAT biology or how DAT regulates the dopaminergic tone, much less how peripheral DAT alters immune function. Our review is guided by the hypothesis that dysfunctional peripheral dopamine signaling might be linked to the dysfunctional immune responses in PD and thereby suggests a potential bidirectional communication between central and peripheral dopamine systems. This review seeks to foster new perspectives concerning PD pathogenesis and progression. |
| Databáze: | OpenAIRE |
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