Neuroinflammation in schizophrenia: the role of nuclear factor kappa B.
Caitlin E MurphyAdam K WalkerCynthia Shannon WeickertPublished in: Translational psychiatry (2021)
Neuroinflammation, particularly in the dorsolateral prefrontal cortex, is well-established in a subset of people with schizophrenia, with significant increases in inflammatory markers including several cytokines. Yet the cause(s) of cortical inflammation in schizophrenia remains unknown. Clues as to potential microenvironmental triggers and/or intracellular deficits in immunoregulation may be gleaned from looking further upstream of effector immune molecules to transcription factors that control inflammatory gene expression. Here, we focus on the 'master immune regulator' nuclear factor kappa B (NF-κB) and review evidence in support of NF-κB dysregulation causing or contributing to neuroinflammation in patients. We discuss the utility of 'immune biotyping' as a tool to analyse immune-related transcripts and proteins in patient tissue, and the insights into cortical NF-κB in schizophrenia revealed by immune biotyping compared to studies treating patients as a single, homogenous group. Though the ubiquitous nature of NF-κB presents several hurdles for drug development, targeting this key immunoregulator with novel or repurposed therapeutics in schizophrenia is a relatively underexplored area that could aid in reducing symptoms of patients with active neuroinflammation.
Keyphrases
- nuclear factor
- toll like receptor
- bipolar disorder
- lps induced
- gene expression
- end stage renal disease
- traumatic brain injury
- prefrontal cortex
- newly diagnosed
- oxidative stress
- ejection fraction
- chronic kidney disease
- lipopolysaccharide induced
- transcription factor
- prognostic factors
- immune response
- dna methylation
- cerebral ischemia
- risk assessment
- cell proliferation
- patient reported
- brain injury
- drug delivery
- depressive symptoms
- transcranial magnetic stimulation
- reactive oxygen species
- dna binding
- physical activity
- high frequency
- patient reported outcomes
- subarachnoid hemorrhage
- case control