Summary: A new study reveals a commonality in gene activity related to the same immune response and inflammatory pathways in the brains of patients with Parkinson’s and Huntington’s disease.
A new study strongly suggests that the brains of people who have died of Huntington’s disease (HD) and Parkinson’s disease (PD) show a similar response to a lifetime of neurodegeneration, despite being two very distinct diseases.
The findings, which appear in the journal Frontiers in Molecular Neuroscience, found that most of the genes perturbed in brains from both diseases are related to the same immune response and inflammatory pathways. Inflammation in the central nervous system has recently been shown to play a role in a number of different neurodegenerative diseases, including HD and PD, but this is the first direct comparison of these two distinct diseases.
Brains of individuals who died with Huntington’s, Parkinson’s or no neurological condition were analyzed using sequencing technology that provides a data readout of the activity of all genes in the genome. By comparing the data from the different groups, the researchers identified which genes show differences in their activity. By organizing and interpreting these genes, the researchers found an overall pattern of commonality between the two diseases. According to the researchers, the hypothesis that the brain experiences a similar response to disparate neurodegenerative diseases has exciting clinical implications. “These findings suggest that a common therapy might be developed to help mitigate the effects of different neurodegenerative diseases of the central nervous system” explained corresponding author Adam Labadorf, PhD, Director of the BU Bioinformatics Hub.
“Though no such treatment yet exists, this finding will lead to experiments to better understand the specific mechanisms of the inflammatory response in the neurodegenerating brain, which may in turn lead to new treatments.”
Labadorf believes that at present, these findings are too preliminary to suggest new clinical treatments. However, as many anti-inflammatory drugs are already available, there may be a relatively short path to designing clinical trials for drugs that modulate the inflammatory response in people with neurodegenerative disease.
“While these findings are specific to HD and PD, these two diseases are sufficiently distinct to suggest that the observed pattern of differential gene activity may likely be observed in other neurodegenerative diseases of the central nervous system, including Alzheimer’s disease and Chronic Traumatic Encephalophathy (CTE).”
About this neuroscience research article
Funding: Funding for this study was provided by grants from US National Institutes of Health (R01-S076843), Characterization of the Role of Cyclin G-associated Kinase in Parkinson Disease, (R01-NS073947), Epigenetic Markers in Huntington’s Disease Brain, (R01-NS088538), An IPSc based platform for functionally assessing genetic and environmental Risk in PD, (U24-NS072026) National Brain and Tissue Resource for Parkinson’s Disease and Related Disorders and the Jerry McDonald Huntington Disease Research Fund.
Source: Gina DiGravio – BMC Publisher: Organized by NeuroscienceNews.com. Image Source: NeuroscienceNews.com image is in the public domain. Original Research: Full open access research for “Evidence for a Pan-Neurodegenerative Disease Response in Huntington’s and Parkinson’s Disease Expression Profiles” by Adam Labadorf, Seung H. Choi, and Richard H. Myers in Frontiers in Molecular Neuroscience. Published online January 11 2017 doi:10.3389/fnmol.2017.00430
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[cbtabs][cbtab title=”MLA”]BMC “Commonalities in the Brains of People With Huntington’s and Parkinson’s Discovered.” NeuroscienceNews. NeuroscienceNews, 12 January 2018. <https://neurosciencenews.com/huntingtons-parkinsons-brains-8305/>.[/cbtab][cbtab title=”APA”]BMC (2018, January 12). Commonalities in the Brains of People With Huntington’s and Parkinson’s Discovered. NeuroscienceNews. Retrieved January 12, 2018 from https://neurosciencenews.com/huntingtons-parkinsons-brains-8305/[/cbtab][cbtab title=”Chicago”]BMC “Commonalities in the Brains of People With Huntington’s and Parkinson’s Discovered.” https://neurosciencenews.com/huntingtons-parkinsons-brains-8305/ (accessed January 12, 2018).[/cbtab][/cbtabs]
Evidence for a Pan-Neurodegenerative Disease Response in Huntington’s and Parkinson’s Disease Expression Profiles
Huntington’s and Parkinson’s Diseases (HD and PD) are neurodegenerative disorders that share some pathological features but are disparate in others. For example, while both diseases are marked by aberrant protein aggregation in the brain, the specific proteins that aggregate and types of neurons affected differ. A better understanding of the molecular similarities and differences between these two diseases may lead to a more complete mechanistic picture of both the individual diseases and the neurodegenerative process in general. We sought to characterize the common transcriptional signature of HD and PD as well as genes uniquely implicated in each of these diseases using mRNA-Seq data from post mortem human brains in comparison to neuropathologically normal controls. The enriched biological pathways implicated by HD differentially expressed genes show remarkable consistency with those for PD differentially expressed genes and implicate the common biological processes of neuroinflammation, apoptosis, transcriptional dysregulation, and neuron-associated functions. Comparison of the differentially expressed (DE) genes highlights a set of consistently altered genes that span both diseases. In particular, processes involving nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) and transcription factor cAMP response element-binding protein (CREB) are the most prominent among the genes common to HD and PD. When the combined HD and PD data are compared to controls, relatively few additional biological processes emerge as significantly enriched, suggesting that most pathways are independently seen within each disorder. Despite showing comparable numbers of DE genes, DE genes unique to HD are enriched in far more coherent biological processes than the DE genes unique to PD, suggesting that PD may represent a more heterogeneous disorder. The complexity of the biological processes implicated by this analysis provides impetus for the development of better experimental models to validate the results.
“Evidence for a Pan-Neurodegenerative Disease Response in Huntington’s and Parkinson’s Disease Expression Profiles” by Adam Labadorf, Seung H. Choi, and Richard H. Myers in Frontiers in Molecular Neuroscience. Published online January 11 2017 doi:10.3389/fnmol.2017.00430