About this Research Topic
Aging is a major risk factor for several neurodegenerative diseases, including Parkinson’s and Alzheimer’s disease. The immune response is often dysregulated in aging, leading to a predisposition towards a state of chronic inflammation. The precise processes which support this inflammatory state are still a subject of debate, however, cell- and tissue-specific transcriptional changes in several immune-related genes have been identified as potential drivers. In addition to genetic changes, losses in the bacterial diversity within the microbiome are also observed during aging. However, it is unclear whether this may be a cause or consequence of inflammation. Host-microbiome interactions are highly complex and are known to modulate the immune response in several ways. For instance, while bacteria and some bacterial byproducts such as short chain fatty acids can induce differentiation of regulatory T cells and stimulate secretion of anti-inflammatory cytokines, other byproducts can activate pathogen recognition receptors to induce inflammation. Bacteria can also regulate the transcription of human genes that regulate immune homeostasis and pathogen response. In turn, microRNAs produced by the gut epithelium can regulate transcription in bacteria.
Importantly, chronic inflammation and dysbiosis are both key features of neurodegenerative diseases. Increased intestinal permeability and dysbiosis in Parkinson’s disease (PD) and Alzheimer’s Disease (AD) patients have prompted studies of LPS induced-inflammation and DSS-induced colitis in mouse models, where pathological features are found to be exacerbated. In a similar vein, allele variants of LRRK2, MHC II, and many others are linked both to a dysregulation of the immune system and to an increased risk developing neurodegenerative diseases. There is also evidence suggesting T-cells, which are auto-reactive to alpha synuclein in PD patients, play a key role in several of the frequently-used Parkinsonian mouse models. Taken together, these recent advances seem to indicate there is an interplay between aging, genetics, the immune system, the microbiome, and neurodegenerative diseases.
With peripheral inflammation as the core tenet, we are interested in investigating how age, genetics, and the microbiome interact with one another and are involved in the initiation and progression of neurodegenerative diseases. We hope that this article collection may not only shed light on disease mechanisms, but also identify new avenues of research that may lead to more effective therapeutic strategies, whether in the form of novel preventative treatments or peripheral biomarkers that can be used to identify early-stage patients. Recent advances across multiple disciplines lend further support to this central aim. For example, the standardization of viral vector mediated gene overexpression and production of preformed fibrils of amyloid proteins have resulted in the development of many new models of neurodegenerative diseases that are more physiologically relevant and capture different disease aspects. In particular, we hope that improvements in molecular biology techniques which allow for high throughput sequencing and omics studies of the immunological landscape will allow for significant progress to be made on this topic.
In this Research Topic, we would like to address the question of how the immune system and activation states of cells change with age, genetics, and environmental exposure, as well as how these correlate with disease stage. Specifically, we are interested in examining how the immune system changes with age, how allele variants which predispose to neurodegenerative diseases affect the immune system, and how exposure to infections and dysbiosis affect the risk of developing neurodegenerative disease. To this aim we welcome Original Research and Review articles focused on the different aspects of peripheral inflammation and neurodegenerative diseases that include but not limited to:
1) In vivo studies describing age-related changes in the microbiome and/or immune response in health and disease.
2) In vitro and in vivo studies examining age- and inflammation-related transcriptional changes of disease-associated genes.
3) In vivo and in vitro studies of the role of the innate and adaptive immune system through the various stages of neurodegenerative disease progression.
4) Registry-based studies examining novel risk factors for neurodegenerative disease, with a particular focus on hospital records of inflammation and infection.
5) Review articles that can put recent advances into a larger context, illuminating areas of interest for future studies.
Importantly, chronic inflammation and dysbiosis are both key features of neurodegenerative diseases. Increased intestinal permeability and dysbiosis in Parkinson’s disease (PD) and Alzheimer’s Disease (AD) patients have prompted studies of LPS induced-inflammation and DSS-induced colitis in mouse models, where pathological features are found to be exacerbated. In a similar vein, allele variants of LRRK2, MHC II, and many others are linked both to a dysregulation of the immune system and to an increased risk developing neurodegenerative diseases. There is also evidence suggesting T-cells, which are auto-reactive to alpha synuclein in PD patients, play a key role in several of the frequently-used Parkinsonian mouse models. Taken together, these recent advances seem to indicate there is an interplay between aging, genetics, the immune system, the microbiome, and neurodegenerative diseases.
With peripheral inflammation as the core tenet, we are interested in investigating how age, genetics, and the microbiome interact with one another and are involved in the initiation and progression of neurodegenerative diseases. We hope that this article collection may not only shed light on disease mechanisms, but also identify new avenues of research that may lead to more effective therapeutic strategies, whether in the form of novel preventative treatments or peripheral biomarkers that can be used to identify early-stage patients. Recent advances across multiple disciplines lend further support to this central aim. For example, the standardization of viral vector mediated gene overexpression and production of preformed fibrils of amyloid proteins have resulted in the development of many new models of neurodegenerative diseases that are more physiologically relevant and capture different disease aspects. In particular, we hope that improvements in molecular biology techniques which allow for high throughput sequencing and omics studies of the immunological landscape will allow for significant progress to be made on this topic.
In this Research Topic, we would like to address the question of how the immune system and activation states of cells change with age, genetics, and environmental exposure, as well as how these correlate with disease stage. Specifically, we are interested in examining how the immune system changes with age, how allele variants which predispose to neurodegenerative diseases affect the immune system, and how exposure to infections and dysbiosis affect the risk of developing neurodegenerative disease. To this aim we welcome Original Research and Review articles focused on the different aspects of peripheral inflammation and neurodegenerative diseases that include but not limited to:
1) In vivo studies describing age-related changes in the microbiome and/or immune response in health and disease.
2) In vitro and in vivo studies examining age- and inflammation-related transcriptional changes of disease-associated genes.
3) In vivo and in vitro studies of the role of the innate and adaptive immune system through the various stages of neurodegenerative disease progression.
4) Registry-based studies examining novel risk factors for neurodegenerative disease, with a particular focus on hospital records of inflammation and infection.
5) Review articles that can put recent advances into a larger context, illuminating areas of interest for future studies.
Keywords: peripheral inflammation, aging, neurodegeneration, Alzheimer's disease, Parkinson's disease, immune response, microbiome, bacteria, T cells, cytokines, pathogen response, dysbiosis, allele variants
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