Chronic Inflammation Links Cancer and Parkinson’s Disease

Li, Zhiming; Zheng, Zaozao; Ruan, Jun; Li, Zhi; Tzeng, Chi-Meng

doi:10.3389/fnagi.2016.00126

Cited by 41 publications

(40 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Acute inflammation is a normal physiological response of the body to harmful stimuli; however, chronic inflammation can severely damage the body and has been directly implicated in a wide range of diseases. 98 The NF-B transcription factor modulates a large variety of genes that are involved in several physiological responses, including inflammatory immune responses, acute-phase inflammatory responses, metastasis, differentiation, and apoptosis. 1 Emerging evidence suggests that NF-B dysregulation is linked to multiple inflammation-related diseases, making NF-B an attractive target for pharmacological intervention.…”

Section: Enhancement Of Tolerance Against Inflammatory Stress By Ginsmentioning

confidence: 99%

Cellular stress response mechanisms as therapeutic targets of ginsenosides

2017

Medicinal Research Reviews

View full text Add to dashboard Cite

Ginseng, one of the most widely used traditional herbal medicines and dietary supplements, has historically been recognized as a tonic herb and adaptogen that can enhance the body's tolerance to various adversities. Ginsenosides are a diverse group of steroidal saponins that comprise the major secondary metabolites of ginseng and are responsible for its multiple pharmacological effects. Emerging evidence suggests that hormetic phytochemicals produced by environmentally stressed plants can activate the moderate cellular stress response mechanisms at a subtoxic level in humans, which may enhance tolerance against severe dysfunction or disease. In this review, we initially describe the role of ginsenosides in the chemical defense of plants from the genus Panax suffering from biotic and abiotic stress. Next, we summarize the diverse evolutionarily conserved cellular stress response pathways regulated by ginsenosides and the subsequent stress tolerance against various dysfunctions or diseases. Finally, the structure-activity relationship involved in the effect of ginsenosides is also analyzed. The evidence presented in this review implicates that ginseng as "the King of all herbs" could be regarded as a well-characterized example of the critical role of cellular stress response mechanisms in understanding the health benefits provided by herbal medicines from an evolutionary and ecological perspective.

show abstract

Section: Enhancement Of Tolerance Against Inflammatory Stress By Ginsmentioning

confidence: 99%

Cellular stress response mechanisms as therapeutic targets of ginsenosides

2017

Medicinal Research Reviews

View full text Add to dashboard Cite

show abstract

“…Activated mast cells release several multifunctional proinflammatory mediators including interleukin-1beta (IL-1β), IL-6, IL-8, IL-17, IL-18, IL-33, tumor necrosis factor-alpha (TNF-α), granulocyte macrophage-colony stimulating factor (GM-CSF), chemokine (C-C motif) ligand 2 (CCL2), CCL5, matrix metalloproteinase-3 (MMP-3), substance P, histamine, tryptase, prostaglandins, reactive oxygen species (ROS), reactive nitrogen species (RNS) and nitric oxide (NO) during an inflammatory response (Mekori and Metcalfe, 2000; Kalesnikoff and Galli, 2008; Sismanopoulos et al, 2012; Theoharides et al, 2012; Kempuraj et al, 2013). Persistent microglial activation and chronic neuroinflammation are implicated in the PD pathogenesis (Grimmig et al, 2016; Li et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

Cross-Talk between Glia, Neurons and Mast Cells in Neuroinflammation Associated with Parkinson’s Disease

Kempuraj

Selvakumar

Zaheer

et al. 2017

J Neuroimmune Pharmacol

View full text Add to dashboard Cite

Parkinson’s disease (PD) is a progressive movement disorder characterized by neuroinflammation and dopaminergic neurodegeneration in the brain. 1-methyl-4-phenylpyridinium (MPP+), a metabolite of the parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces the release of inflammatory mediators from glial cells and neurons. Glia maturation factor (GMF), a brain proinflammatory protein, MPP+, and mast cell-derived inflammatory mediators induce neurodegeneration which eventually leads to PD. However, the precise mechanisms underlying interaction between glial cells, neurons and mast cells in PD still remain elusive. In the present study, mouse bone marrow-derived mast cells (BMMCs) and mouse fetal brain-derived mixed glia/neurons, astrocytes and neurons were incubated with MPP+, GMF and mast cell-derived inflammatory mediators mouse mast cell protease-6 (MMCP-6), MMCP-7 or tryptase/brain-specific serine protease-4 (tryptase/BSSP-4). Inflammatory mediators released from these cells in the culture medium were quantitated by enzyme-linked immunosorbent assay. Neurodegeneration was quantified by measuring total neurite outgrowth following microtubule-associated protein-2 immunocytochemistry. MPP+− induced significant neurodegeneration with reduced total neurite outgrowth. MPP+− induced the release of tryptase/BSSP-4 from the mouse mast cells, and tryptase/BSSP-4 induced chemokine (C-C motif) ligand 2 (CCL2) release from astrocytes and glia/neurons. Overall our results suggest that MPP+, GMF, MMCP-6 or MMCP-7 stimulate glia/neurons, astrocytes or neurons to release CCL2 and matrix metalloproteinase-3. Additionally, CD40L expression is increased in BMMCs after incubation with MPP+ in a co-culture system consisting of BMMCs and glia/neurons. We propose that mast cell interaction with glial cells and neurons during neuroinflammation can be explored as a new therapeutic target for PD.

show abstract

“…The hypothesis is that PD and cancer share important common signalling pathway, namely DNA repair and apoptosis,37 and inefficient DNA repair and ageing-related disorder in PD are considered the key factor resulting in cancer 38. In fact, recent study gave good hints on how chronic inflammation links cancer and PD 39. Therefore, it is not complicated to understand exhausted T cells from either CHB or HCC shared a large portion of genes related to PD.…”

Section: Discussionmentioning

confidence: 99%

T cell dysfunction in chronic hepatitis B infection and liver cancer: evidence from transcriptome analysis

et al. 2018

View full text Add to dashboard Cite

BackgroundT cell dysfunction occurs in many diseases, especially in chronic virus infection and cancers. However, up to now, little is known on the distinctions in T cell exhaustion between cancer and chronic virus infection. The objective of this study is to explore the transcriptional similarities and differences in exhausted CD8 +T cell between chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC).MethodsRNA sequencing was performed to compare the transcriptome of CD8 +T cells isolated from healthy donors’ blood, tumour tissues of patients with HCC and chronic HBV infected HCC patients’ paracancerous tissues. DESeq2 algorithm was used to determine differentially expressed genes. Gene ontology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted for in-depth analysis of these differentially expressed genes.ResultsA total number of 2109 and 2203 genes were differentially expressed in patients with chronic HBV infection and HCC, respectively. Comparing these two groups of differentially deregulated genes, we found that nearly half of them were shared, and these shared genes were further classified into several functional categories, such as metabolic process, binding and intracellular organelle. KEGG analysis revealed that these shared deregulated genes were involved in many important pathways such as Parkinson’s disease, oxidative phosphorylation and messenger RNA surveillance. Interestingly, we reported that chronic HBV infection specific deregulated genes were mainly enriched in graft versus host disease, allograft rejection, phenylalanine, tyrosine and tryptophan biosynthesis pathways. Whereas, HCC-specific deregulated genes were highly enriched in oxidative phosphorylation, thyroid cancer and endometrial cancer pathways.ConclusionOur study demonstrated that T cell dysfunction associated with HCC and chronic HBV infection shares high similarities, however, each possesses its own features in terms of specific genes and signalling pathways. Uncovering the differences of T cells dysfunction would facilitate our understanding the diseases pathogenesis and developing innovative therapies in the future.

show abstract

Chronic Inflammation Links Cancer and Parkinson’s Disease

Cited by 41 publications

References 48 publications

Cellular stress response mechanisms as therapeutic targets of ginsenosides

Cellular stress response mechanisms as therapeutic targets of ginsenosides

Cross-Talk between Glia, Neurons and Mast Cells in Neuroinflammation Associated with Parkinson’s Disease

T cell dysfunction in chronic hepatitis B infection and liver cancer: evidence from transcriptome analysis

Contact Info

Product

Resources

About