Targeting of the class II transactivator attenuates inflammation and neurodegeneration in an alpha-synuclein model of Parkinson's disease

Journal of Neuroinflammation
Gregory P WilliamsAshley S Harms

Abstract

Parkinson's disease (PD) is characterized by intracellular alpha-synuclein (α-syn) inclusions, progressive death of dopaminergic neurons in the substantia nigra pars compacta (SNpc), and activation of the innate and adaptive immune systems. Disruption of immune signaling between the central nervous system (CNS) and periphery, such as through targeting the chemokine receptor type 2 (CCR2) or the major histocompatibility complex II (MHCII), is neuroprotective in rodent models of PD, suggesting a key role for innate and adaptive immunity in disease progression. The purpose of this study was to investigate whether genetic knockout or RNA silencing of the class II transactivator (CIITA), a transcriptional co-activator required for MHCII induction, is effective in reducing the neuroinflammation and neurodegeneration observed in an α-syn mouse model of PD. In vitro, we utilized microglia cultures from WT or CIITA -/- mice treated with α-syn fibrils to investigate inflammatory iNOS expression and antigen processing via immunocytochemistry (ICC). In vivo, an adeno-associated virus (AAV) was used to overexpress α-syn in WT and CIITA -/- mice as a model for PD. Concurrently with AAV-mediated overexpression of α-syn, WT mice received CIITA...Continue Reading

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Citations

Oct 4, 2020·Movement Disorders : Official Journal of the Movement Disorder Society·Ashley S HarmsRobert H Mach
Jan 30, 2020·Acta Neuropathologica·Gregory P WilliamsAshley S Harms
Apr 26, 2020·Nature Reviews. Neurology·Eng-King TanJoseph Jankovic
Feb 2, 2019·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Sireesha ManneAnumantha G Kanthasamy
Feb 2, 2020·Brain, Behavior, and Immunity·Ruwani S WijeyekoonCaroline H Williams-Gray
Feb 9, 2021·Acta Neuropathologica·Ashley S HarmsMarina Romero-Ramos
Feb 14, 2021·Journal of Parkinson's Disease·Sonia GeorgePatrik Brundin
Feb 13, 2021·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Tai WangYuming Xu
Mar 4, 2021·Immunity, Inflammation and Disease·Bingnan LiuRong Fu
Apr 15, 2021·NPJ Parkinson's Disease·Samantha M CarlisleDavid G Standaert
Mar 12, 2021·Brain : a Journal of Neurology·Gregory P WilliamsAshley S Harms
Sep 1, 2021·Neurobiology of Disease·Robert BrendzaBrad A Friedman

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Methods Mentioned

BETA
genetic knockout
Transfection
dissector
genetic knock-out
flow cytometry
flow

Software Mentioned

MicroBrightfield
ImageJ
StereoInvestigator
FlowJo

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