Microglia-specific knock-out of NF-κB/IKK2 increases the accumulation of misfolded α-synuclein through the inhibition of p62/sequestosome-1-dependent autophagy in the rotenone model of Parkinson's disease.

Authors

• Savannah M Rocha
• Kelly S Kirkley
• Debotri Chatterjee
• Tawfik A Aboellail
• Richard J Smeyne
• Ronald B Tjalkens

Publication/Presentation Date

9-1-2023

Abstract

Parkinson's disease (PD) is the most common neurodegenerative movement disorder worldwide, with a greater prevalence in men than women. The etiology of PD is largely unknown, although environmental exposures and neuroinflammation are linked to protein misfolding and disease progression. Activated microglia are known to promote neuroinflammation in PD, but how environmental agents interact with specific innate immune signaling pathways in microglia to stimulate conversion to a neurotoxic phenotype is not well understood. To determine how nuclear factor kappa B (NF-κB) signaling dynamics in microglia modulate neuroinflammation and dopaminergic neurodegeneration, we generated mice deficient in NF-κB activation in microglia (CX3CR1-Cre::IKK2

Volume

71

Issue

9

First Page

2154

Last Page

2179

ISSN

1098-1136

Published In/Presented At

Rocha, S. M., Kirkley, K. S., Chatterjee, D., Aboellail, T. A., Smeyne, R. J., & Tjalkens, R. B. (2023). Microglia-specific knock-out of NF-κB/IKK2 increases the accumulation of misfolded α-synuclein through the inhibition of p62/sequestosome-1-dependent autophagy in the rotenone model of Parkinson's disease. Glia, 71(9), 2154–2179. https://doi.org/10.1002/glia.24385

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

37199240

Department(s)

Administration and Leadership

Document Type

Article