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Review
. 2018 Sep 11:12:626.
doi: 10.3389/fnins.2018.00626. eCollection 2018.

α-Synuclein and Noradrenergic Modulation of Immune Cells in Parkinson's Disease Pathogenesis

Laura M Butkovich  1 , Madelyn C Houser  1 , Malú G Tansey  1
Affiliations
Review

α-Synuclein and Noradrenergic Modulation of Immune Cells in Parkinson's Disease Pathogenesis

Laura M Butkovich et al. Front Neurosci. .

Abstract

α-synuclein (α-syn) pathology and loss of noradrenergic neurons in the locus coeruleus (LC) are among the most ubiquitous features of Parkinson's disease (PD). While noradrenergic dysfunction is associated with non-motor symptoms of PD, preclinical research suggests that the loss of LC norepinephrine (NE), and subsequently its immune modulatory and neuroprotective actions, may exacerbate or even accelerate disease progression. In this review, we discuss the mechanisms by which α-syn pathology and loss of central NE may directly impact brain health by interrupting neurotrophic factor signaling, exacerbating neuroinflammation, and altering regulation of innate and adaptive immune cells.

Keywords: Parkinson’s disease; immune cell; locus coeruleus; neuroinflammation; norepinephrine; α-synuclein.

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Figures

FIGURE 1
FIGURE 1
Potential effects of dysregulated NE in PD. Abbreviations: α-syn, α-synuclein; BBB, blood brain barrier; B cell, B lymphocytes; BDNF, brain derived neurotrophic factor; LC, locus coeruleus; PD, Parkinson’s disease; NE, norepinephrine; Th1, T helper 1 lymphocytes; Th17, IL-17 producing T helper lymphocytes; Th2, T helper 2 lymphocytes; CD8+, cytotoxic T lymphocytes; Treg, T regulatory lymphocytes; Trkb, tropomyosin-related kinase B receptor.
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