Advances in NURR1-Regulated Neuroinflammation Associated with Parkinson's Disease.
Murad Al-NusaifYushan LinTianbai LiCheng ChengWeidong LePublished in: International journal of molecular sciences (2022)
Neuroinflammation plays a crucial role in the progression of neurodegenerative disorders, particularly Parkinson's disease (PD). Glial cell activation and subsequent adaptive immune involvement are neuroinflammatory features in familial and idiopathic PD, resulting in the death of dopaminergic neuron cells. An oxidative stress response, inflammatory mediator production, and immune cell recruitment and activation are all hallmarks of this activation, leading to chronic neuroinflammation and progressive neurodegeneration. Several studies in PD patients' cerebrospinal fluid and peripheral blood revealed alterations in inflammatory markers and immune cell populations that may lead to or exacerbate neuroinflammation and perpetuate the neurodegenerative process. Most of the genes causing PD are also expressed in astrocytes and microglia, converting their neuroprotective role into a pathogenic one and contributing to disease onset and progression. Nuclear receptor-related transcription factor 1 (NURR1) regulates gene expression linked to dopaminergic neuron genesis and functional maintenance. In addition to playing a key role in developing and maintaining neurotransmitter phenotypes in dopaminergic neurons, NURR1 agonists have been shown to reverse behavioral and histological abnormalities in animal PD models. NURR1 protects dopaminergic neurons from inflammation-induced degeneration, specifically attenuating neuronal death by suppressing the expression of inflammatory genes in microglia and astrocytes. This narrative review highlights the inflammatory changes in PD and the advances in NURR1-regulated neuroinflammation associated with PD. Further, we present new evidence that targeting this inflammation with a variety of potential NURR1 target therapy medications can effectively slow the progression of chronic neuroinflammation-induced PD.
Keyphrases
- cerebral ischemia
- lipopolysaccharide induced
- oxidative stress
- traumatic brain injury
- transcription factor
- gene expression
- lps induced
- cognitive impairment
- inflammatory response
- peripheral blood
- spinal cord
- end stage renal disease
- stem cells
- ejection fraction
- multiple sclerosis
- newly diagnosed
- neuropathic pain
- induced apoptosis
- genome wide
- drug induced
- risk assessment
- signaling pathway
- spinal cord injury
- brain injury
- subarachnoid hemorrhage
- single cell
- endothelial cells
- mesenchymal stem cells
- human health
- pi k akt