Trends in Molecular Medicine
ReviewParkinson's disease in the nuclear age of neuroinflammation
Section snippets
Parkinson's disease
Parkinson's disease (PD) is a common neurodegenerative disease characterised primarily by the deterioration of motor activities that are controlled by the nigrostriatal system (Box 1). The resulting symptoms include tremors at rest, rigidity, bradykinesia, and postural instability [1]. Pathologically, PD is identified by the death of dopaminergic neurons which project from the substantia nigra (SN) to the striatum, leading to a marked decrease in dopaminergic neurotransmission to the striatum;
Nuclear hormone receptors involved in inflammation – potential therapeutic targets for Parkinson's disease?
Nuclear receptors (NRs) are ligand-activated transcription factors that regulate genes involved in physiological, metabolic, and developmental processes through their association with sequence-specific elements within the promoter regions of their target genes. Thus, they mediate transcriptional responses to hormones and other metabolic ligands. Several ligands of NRs are now in therapeutic use for breast cancer, diabetes, and inflammatory disorders. Recent investigations show that certain NRs
Concluding remarks
Therapeutic intervention for PD remains a major challenge. The rapidly emerging evidence that inflammation significantly contributes to the pathology of the disease places neuroinflammation as an important focus of research in PD, and consequently positions immunomodulatory therapies as prime targets for investigation. Specifically, approaches targeting the NRs that we have discussed here are proving particularly promising (Table 2). It is especially encouraging that some of these, such as
Acknowledgement
We apologise to all authors whose work in this field has not been cited owing to space limitations. We are grateful to John Cryan, Ian O’Brien, and Louise Collins for their helpful discussions.
Glossary
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
- a chemical precursor to a neurotoxin that destroys dopaminergic neurons. In primates and mice, MPTP can be administered peripherally to produce laboratory models of PD. MPTP is not itself toxic, but it crosses the blood–brain barrier and is converted to the toxic cation 1-methyl-4-phenylpyridinium (MPP+) by the enzyme monoamine oxidase (MAO)-B in glial cells. MPP+ is taken up by dopaminergic neurons via the dopamine transporter protein on the
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Nuclear orphan receptors: A novel therapeutic agent in neuroinflammation
2023, International ImmunopharmacologyMedicinal Plants for Anti-neurodegenerative diseases in West Africa
2022, Journal of EthnopharmacologyCitation Excerpt :Genomic studies have implied about 28 genes directly or indirectly associated with PD. Their pathogeneses include mitochondrial dysfunction, endoplasmic reticulum stress, autophagy, inflammation and impaired insulin signalling (Hinchcliffe et al., 2008; Moreira et al., 2010; Mercado et al., 2013; Nolan et al., 2013; Lin and Farrer, 2014). For instance, Okubadejo et al. (2006) reported the first PD gene screening in Nigeria, West Africa with no pathogenic mutation in the gene related to PD.