The immune system on the TRAIL of Alzheimer’s disease

Burgaletto, Chiara; Munafò, Antonio; Benedetto, Giulia Di; Francisci, Cettina De; Caraci, Filippo; Mauro, Rosaria Di; Bucolo, Claudio; Bernardini, Renato; Cantarella, Giuseppina

doi:10.1186/s12974-020-01968-1

Cited by 54 publications

(44 citation statements)

References 139 publications

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“…Enrichment analysis was then performed based on each of the shortest paths, the special functions (i.e., the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and the Biological Process (BP) term in Gene Ontology (GO), shown in Figure 5 and Table 5 ). These indicated multiple dysfunctions of different ND types ( McGeer et al, 1989 ; Behl, 2000 ; Nagatsu et al, 2000 ; Everse et al, 2011 ; Obulesu and Lakshmi, 2014 ; Caputi and Giron, 2018 ; Cui and Xu, 2018 ; Yan et al, 2018 ; Liu et al, 2019 ; Porro et al, 2019 ; Starr, 2019 ; Ashrafizadeh et al, 2020 ; Burgaletto et al, 2020 ; Luo et al, 2020 ; Paul et al, 2021 ), respectively.…”

Section: Resultsmentioning

confidence: 99%

Comparative Analysis of Multiple Neurodegenerative Diseases Based on Advanced Epigenetic Aging Brain

Shi

Chen

et al. 2021

Front. Genet.

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Background: Neurodegenerative Diseases (NDs) are age-dependent and include Alzheimer’s disease (AD), Parkinson’s disease (PD), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), and so on. There have been numerous studies showing that accelerated aging is closely related (even the driver of) ND, thus promoting imbalances in cellular homeostasis. However, the mechanisms of how different ND types are related/triggered by advanced aging are still unclear. Therefore, there is an urgent need to explore the potential markers/mechanisms of different ND types based on aging acceleration at a system level.Methods: AD, PD, PSP, FTD, and aging markers were identified by supervised machine learning methods. The aging acceleration differential networks were constructed based on the aging score. Both the enrichment analysis and sensitivity analysis were carried out to investigate both common and specific mechanisms among different ND types in the context of aging acceleration.Results: The extracellular fluid, cellular metabolisms, and inflammatory response were identified as the common driving factors of cellular homeostasis imbalances during the accelerated aging process. In addition, Ca ion imbalance, abnormal protein depositions, DNA damage, and cytoplasmic DNA in macrophages were also revealed to be special mechanisms that further promote AD, PD, PSP, and FTD, respectively.Conclusion: The accelerated epigenetic aging mechanisms of different ND types were integrated and compared through our computational pipeline.

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Section: Resultsmentioning

confidence: 99%

Comparative Analysis of Multiple Neurodegenerative Diseases Based on Advanced Epigenetic Aging Brain

Shi

Chen

et al. 2021

Front. Genet.

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“…Chronic neuroinflammation is one of the main leitmotiv driving current hypotheses in support of the pathogenesis of AD (Scuderi et al, 2020). Such phenomenon largely derives from aberrant activation of microglia, the brain resident mononuclear phagocytes physiologically involved in central immune surveillance and clearance of pathogens (Burgaletto et al, 2020;Ní Chasaide and Lynch, 2020).…”

Section: Introductionmentioning

confidence: 99%

Repositioning of Immunomodulators: A Ray of Hope for Alzheimer’s Disease?

et al. 2020

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Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder characterized by cognitive decline and by the presence of amyloid β plaques and neurofibrillary tangles in the brain. Despite recent advances in understanding its pathophysiological mechanisms, to date, there are no disease-modifying therapeutic options, to slow or halt the evolution of neurodegenerative processes in AD. Current pharmacological treatments only transiently mitigate the severity of symptoms, with modest or null overall improvement. Emerging evidence supports the concept that AD is affected by the impaired ability of the immune system to restrain the brain’s pathology. Deep understanding of the relationship between the nervous and the immune system may provide a novel arena to develop effective and safe drugs for AD treatment. Considering the crucial role of inflammatory/immune pathways in AD, here we discuss the current status of the immuno-oncological, immunomodulatory and anti-TNF-α drugs which are being used in preclinical studies or in ongoing clinical trials by means of the drug-repositioning approach.

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“…These results supported the neuroimmunopathogenesis of AD. In recent years, AD has no longer been considered a neural-centric disease, and the critical role played by neuroinflammation in the pathogenesis of AD has been implicated in many genetic, functional, and neuroimaging studies (Cao and Zheng, 2018;Jansen et al, 2019;Kunkle et al, 2019;Passamonti et al, 2019;Bis et al, 2020;Burgaletto et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Preservation Analysis on Spatiotemporal Specific Co-expression Networks Suggests the Immunopathogenesis of Alzheimer’s Disease

Guo

Liu

Wang

2021

Front. Aging Neurosci.

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The occurrence and development of Alzheimer’s disease (AD) is a continuous clinical and pathophysiological process, molecular biological, and brain functional change often appear before clinical symptoms, but the detailed underlying mechanism is still unclear. The expression profiling of postmortem brain tissue from AD patients and controls provides evidence about AD etiopathogenesis. In the current study, we used published AD expression profiling data to construct spatiotemporal specific coexpression networks in AD and analyzed the network preservation features of each brain region in different disease stages to identify the most dramatically changed coexpression modules and obtained AD-related biological pathways, brain regions and circuits, cell types and key genes based on these modules. As result, we constructed 57 spatiotemporal specific networks (19 brain regions by three disease stages) in AD and observed universal expression changes in all 19 brain regions. The eight most dramatically changed coexpression modules were identified in seven brain regions. Genes in these modules are mostly involved in immune response-related pathways and non-neuron cells, and this supports the immune pathology of AD and suggests the role of blood brain barrier (BBB) injuries. Differentially expressed genes (DEGs) meta-analysis and protein–protein interaction (PPI) network analysis suggested potential key genes involved in AD development that might be therapeutic targets. In conclusion, our systematical network analysis on published AD expression profiling data suggests the immunopathogenesis of AD and identifies key brain regions and genes.

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The immune system on the TRAIL of Alzheimer’s disease

Cited by 54 publications

References 139 publications

Comparative Analysis of Multiple Neurodegenerative Diseases Based on Advanced Epigenetic Aging Brain

Comparative Analysis of Multiple Neurodegenerative Diseases Based on Advanced Epigenetic Aging Brain

Repositioning of Immunomodulators: A Ray of Hope for Alzheimer’s Disease?

Preservation Analysis on Spatiotemporal Specific Co-expression Networks Suggests the Immunopathogenesis of Alzheimer’s Disease

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