Research Topic

Infection, Inflammation, Cardiovascular diseases and Neurodegeneration

About this Research Topic

Alzheimer's disease (AD), the most prevalent neurodegenerative disorder, has been a primary focus of current research in Neuroscience and Neurology. These last decades, great signs of progress have been made in the comprehension of AD physiopathology. According to the well-known “amyloid hypothesis”, amyloid ...

Alzheimer's disease (AD), the most prevalent neurodegenerative disorder, has been a primary focus of current research in Neuroscience and Neurology. These last decades, great signs of progress have been made in the comprehension of AD physiopathology. According to the well-known “amyloid hypothesis”, amyloid beta and phosphorylated tau, which aggregate in plaques and tangles respectively, are the two most characteristic pathological causes and hallmarks of AD. However, most therapeutic attempts for reversing AD based on these previous pieces of knowledge have failed, in part because the etiology of AD is not yet completely understood. Identification of the disease cause is of utmost importance for the development of valid preventative and therapeutic strategies.

Genomic features are fundamental factors impacting human phenotype. Mutations in three genes APP, PSEN1, and PSEN2 were identified to be the cause of some familial early-onset AD. In sporadic AD, genome-wide association studies (GWASs) and next-generation sequencing (NGS) studies have identified numerous genetic variants associated with an increased risk of AD. In particular, a large proportion of these risk genes, such as CD33, CLU, CR1, TREM2, and C7, are actively involved in immune mechanisms. This suggests a potential important role of the immune pathways in AD etiology.

Many types of microbes, including virus (e.g. herpes simplex virus [HSV]) and bacterium (e.g. Chlamydophila pneumoniae and Porphyromonas gingivalis) have been found in AD patient brains. Most recent findings reported that these pathogen infections directly contribute to the development of AD. For instance, plaque-like beta amyloid deposits were observed in mice following inhalation of C. pneumoniae; and accumulation of amyloid beta and phosphorylation of tau is induced in neurons infected by HSV-1. Consistently, amyloid beta is recognized to be an antimicrobial peptide that protects against fungal, bacterial, and viral infections. In the brain of mice infected with salmonella, there is plaque formation; and those mice with plaque lived longer than mice that didn't develop the plaques.

Hypothesis- based on these findings, some researchers suggested that a single microbe -- a virus, bacterium, or fungus might be found at the center of the plaque. Thus, the development of amyloid beta plaques in the brain might have a protective response role to brain infection. In addition, a peripheral infection might also contribute to dementia due to systemic inflammation. These hypothesis point to an infectious etiology of AD. Following these, “the amyloid hypothesis observations” might reflect a protective mechanism and not only be the primary cause of the disease.

Like in Alzheimer’s disease, we can observe some immune genes involved in genetic risk of some other neurodegenerative diseases such as Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). A good example is TBK1, a key gene in the NF-kappa-B pathway, was identified to be pathogenic gene for ALS and FTD. Considering that AD shares several symptomatic and morphological features with other neurodegenerative diseases, the presented “pathogen hypothesis” might offer an explanation to the start of protein aggregation in neurodegeneration. This could change the current dogma in neurodegeneration and possibly open new fronts to understand neurodegenerative processes.

Although the pathogen hypothesis is not a new idea, it is grossly underemphasized in basic researches and clinical strategies. This Research Topic aims to investigate a potential link between pathogens and the onset of neurodegeneration. The current priorities for research in the emerging field might include:

• What are the endogenous microbes in healthy brains and is there any difference with neurodegenerative patients’ brain, as addressed by efforts such as the Brain Microbiome Project;
• Is there a common pathogen specificity for each neurodegenerative disorder? Or any type of infection that dysregulated the brain microbiome might be the cause?
• What role do genetic risk alleles play in the neurodegeneration-related infection?
• Will therapeutic approaches that take infectious causes into account make sense?

To gain focus on the role of pathogens in neurodegeneration, we welcome all types of contribution (Original Research, Review, Perspective) from related research areas such as disease modeling, human neuropathology or therapeutic interventions.


Topic Editor Dr. Gjumrakch Aliev is the President of the “GALLY” International Biomedical Research Institute Inc. The other Topic Editors declare no competing interests with regards to the Research Topic.


Keywords: Alzheimer's disease, Infection, Inflammation, Microbiome


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

11 August 2020 Manuscript

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Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

11 August 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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