NF-κB activity is inversely correlated to RNF11 expression in Parkinson's disease

Abstract

RING finger protein 11 (RNF11), a negative regulator of NF-κB signaling pathway, colocalizes with α-synuclein and is sequestered in Lewy bodies in Parkinson’s disease (PD). Since persistent NF-κB activation is reported in PD, in this report we investigated if RNF11 expression level is correlated to activated NF-κB in PD. We examined RNF11 expression levels in correlation to phospho-p65, a marker for activated NF-κB, in control and PD brain tissue from cerebral cortex. In addition we performed double immunofluorescence labeling experiments to confirm this correlation. Our investigations demonstrated that the neuronal RNF11 expression was down-regulated in PD and was usually associated with increased expression of phospho-p65. Double labeling confirmed that loss of neuronal RNF11 was linked to increased phospho-p65 expression, suggesting that persistent presence of NF-κB activation could be due to decreased levels of its negative regulator. Our data exemplifies the relevance of RNF11 and persistent NF-κB activation in PD.

Farrerol attenuates MPP+‐induced inflammatory response by TLR4 signaling in a microglia cell line

“…The pro‐inflammatory cytokines secreted by microglia cells such as IL‐1β and TNF‐α may directly bind to cytokine receptors that locate on the surface of DA neurons, thereby triggering the activation of NF‐κB, eventually leading to DA neuron degeneration through apoptotic cell death (Phani, Loike, & Przedborski, ). Notably, NF‐κB expression is highly elevated in brain samples from PD patients (Pranski et al, ). Based on in vitro studies, it has been found that NF‐κB activation is triggered by MPP + in BV‐2 cells.…”

Neuroprotective Effects of Sulphated Agaran from Marine Alga Gracilaria cornea in Rat 6‐Hydroxydopamine Parkinson's Disease Model: Behavioural, Neurochemical and Transcriptional Alterations

“…The enhanced production of free radicals is a major determinant in the transcriptional activation of nuclear factor kappa B (NFkB). p65 subunit (p65) is the main constituent protein and a marker for the nuclear factor kappa B (NFkB), which is considered the master transcriptional regulator of the inflammatory process and is associated with the neurodegenerative mechanism in animal models induced by 6‐OHDA and other neurotoxins such as rotenone and MPTP . Moreover, NFkB up‐regulates the transcription of several genes, including interleukin‐1β (IL‐1β) and inducible nitric oxide synthase (iNOS) .…”

Inflammatory response in Parkinson’s disease (Review)

“…Pyrrolidine dithiocarbamate (PDTC), another NF-κB inhibitor, significantly ameliorated the DA deficits induced by MPTP in wild-type mice, where MPTP treatment significantly increased oxidative damage. Consistently, PDTC significantly attenuated MPTP-induced behavioral impairments in wild-type mice (124). Activated NF-κB expression levels were significantly increased in the striatum of MPTP-treated PD mouse models (125).…”