Systems Biology Approaches to Understand the Host–Microbiome Interactions in Neurodegenerative Diseases

Rosário, Dorinês; Borén, Jan; Uhlén, Mathias; Proctor, Gordon; Aarsland, Dag; Mardinoğlu, Adil; Shoaie, Saeed

doi:10.3389/fnins.2020.00716

Cited by 50 publications

(34 citation statements)

References 145 publications

(364 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This acute inflammation is at the very beginning a protective process, meant to contain the damaging effects of this injury. 8 The proper characteristic of this inflammation is to produce an immune reaction which will normally eliminate the damaging effects of the insult. This will mobilize the innate immune system first to produce pro-inflammatory cytokines as well as antimicrobial peptides.…”

Section: What Is Alzheimer’s Disease?mentioning

confidence: 99%

“…The occurrence of dysbiosis/pathobiont 276 may be prevented since the earliest period of life by a diet maintaining gut microbiota health. 8 In this context, a balanced anti-inflammatory diet such as the Mediterranean or the Asian diet may be successful candidates. 277–283 In contrast to the western diet, these diets contain many beneficial products maintaining a balanced inflammatory milieu even during aging when the inflammaging is very frequent.…”

Section: What About Interventions?mentioning

confidence: 99%

See 1 more Smart Citation

Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

Fülöp¹,

Tripathi²,

Rodrigues³

et al. 2021

NDT

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is the most common form of dementia and aging is the most common risk factor for developing the disease. The etiology of AD is not known but AD may be considered as a clinical syndrome with multiple causal pathways contributing to it. The amyloid cascade hypothesis, claiming that excess production or reduced clearance of amyloid-beta (Aβ) and its aggregation into amyloid plaques, was accepted for a long time as the main cause of AD. However, many studies showed that Aβ is a frequent consequence of many challenges/pathologic processes occurring in the brain for decades. A key factor, sustained by experimental data, is that low-grade infection leading to production and deposition of Aβ, which has antimicrobial activity, precedes the development of clinically apparent AD. This infection is chronic, low grade, largely clinically silent for decades because of a nearly efficient antimicrobial immune response in the brain. A chronic inflammatory state is induced that results in neurodegeneration. Interventions that appear to prevent, retard or mitigate the development of AD also appear to modify the disease. In this review, we conceptualize further that the changes in the brain antimicrobial immune response during aging and especially in AD sufferers serve as a foundation that could lead to improved treatment strategies for preventing or decreasing the progression of AD in a disease-modifying treatment.

show abstract

Section: What Is Alzheimer’s Disease?mentioning

confidence: 99%

Section: What About Interventions?mentioning

confidence: 99%

Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

Fülöp¹,

Tripathi²,

Rodrigues³

et al. 2021

NDT

View full text Add to dashboard Cite

show abstract

“…To elucidate these interactions, individual-and systems-level analysis is required. Therefore, systems biology approaches could be applied to reveal associations between the abundances of different microbes and the molecular mechanisms underlying PD on a functional level (Witherden et al, 2017;Mardinoglu et al, 2018;Rosario et al, 2020). Genome-scale metabolic models (GEMs) have been applied to gain detailed understanding of microbial metabolic changes in different environments (Gu et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Systematic analysis of gut microbiome reveals the role of bacterial folate and homocysteine metabolism in Parkinson’s disease

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…The life span of marmosets in captivity can be as long as 10 to 15 years, making these animals a suitable model for research into aging 27 . As their immune systems and metabolic functions resemble those of humans, 27,28 the pathogenic processes related to AD may thus be similarly affected 29–31 . Because sleep disorder is an early clinical symptom of AD 32 , it is noteworthy that marmosets share similar sleep phases with humans, as evidenced by the presence of rapid eye movement (REM) and non-REM cycles 33 .…”

Section: Introductionmentioning

confidence: 99%

A non-human primate model of familial Alzheimer’s disease

Sato¹,

Sasaguri

Kumita

et al. 2020

Preprint

View full text Add to dashboard Cite

Alzheimer's disease (AD) is a major cause of dementia, with the number of patients with this condition anticipated to exceed 50 million worldwide in the near future. Despite extensive research efforts, no effective measures are available to facilitate the prevention or treatment of AD, which is due in part to a lack of animal models able to closely replicate a human-like disease state. Here, we describe the generation of three mutant marmoset individuals in which exon 9 of PSEN1 gene product has been deleted (PSEN1-DeltaE9). Such DeltaE9 mutations have been reported to cause early on-set familial AD (references 1-5). We used Transcription Activator-Like Effector Nuclease (TALEN) to destroy the 3' splice site of exon 9 in the marmoset PSEN1 gene. To this end, TALEN exhibits high genome-editing efficacy, generates few off-target effects, and produces minimal mosaicism. Indeed, whole genome sequencing and other analyses illustrated an absence of off-target effects and an apparent absence of mosaicism. Fibroblasts obtained from newborn marmosets exhibited uncleaved full-length presenilin 1 protein (PS1) caused by the perturbation of PS1 endoproteolysis as well as an increased ratio of Abeta42/Abeta40 production, a signature of familial AD pathogenesis. To our knowledge, this is the first non-human primate model of familial AD. We intend to make our marmoset model available to the research community to facilitate the global fight against AD.

show abstract

Systems Biology Approaches to Understand the Host–Microbiome Interactions in Neurodegenerative Diseases

Cited by 50 publications

References 145 publications

Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

Systematic analysis of gut microbiome reveals the role of bacterial folate and homocysteine metabolism in Parkinson’s disease

A non-human primate model of familial Alzheimer’s disease

Contact Info

Product

Resources

About