Alzheimer's disease, autoimmunity and inflammation. The good, the bad and the ugly

Sardi, F.; Fassina, Lorenzo; Venturini, Letizia; Inguscio, M.; Guerriero, F.; Rolfo, E.; Ricevuti, Giovanni

doi:10.1016/j.autrev.2011.09.005

Cited by 161 publications

(122 citation statements)

References 67 publications

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“…In the brain of patients suffering from neurodegenerative diseases [138][139][140] and in animal models of these disorders [141][142][143][144], signs of massive neuroinflammation are detected. Importantly, the phenotype of both astrocytes and microglia changes in ageing.…”

Section: Processes Contributing To Brain Ageingmentioning

confidence: 99%

The endocannabinoid system in normal and pathological brain ageing

Bilkei-Gorzó

2012

Phil. Trans. R. Soc. B

121

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The role of endocannabinoids as inhibitory retrograde transmitters is now widely known and intensively studied. However, endocannabinoids also influence neuronal activity by exerting neuroprotective effects and regulating glial responses. This review centres around this less-studied area, focusing on the cellular and molecular mechanisms underlying the protective effect of the cannabinoid system in brain ageing. The progression of ageing is largely determined by the balance between detrimental, proageing, largely stochastic processes, and the activity of the homeostatic defence system. Experimental evidence suggests that the cannabinoid system is part of the latter system. Cannabinoids as regulators of mitochondrial activity, as anti-oxidants and as modulators of clearance processes protect neurons on the molecular level. On the cellular level, the cannabinoid system regulates the expression of brainderived neurotrophic factor and neurogenesis. Neuroinflammatory processes contributing to the progression of normal brain ageing and to the pathogenesis of neurodegenerative diseases are suppressed by cannabinoids, suggesting that they may also influence the ageing process on the system level. In good agreement with the hypothesized beneficial role of cannabinoid system activity against brain ageing, it was shown that animals lacking CB1 receptors show early onset of learning deficits associated with age-related histological and molecular changes. In preclinical models of neurodegenerative disorders, cannabinoids show beneficial effects, but the clinical evidence regarding their efficacy as therapeutic tools is either inconclusive or still missing.

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Section: Processes Contributing To Brain Ageingmentioning

confidence: 99%

The endocannabinoid system in normal and pathological brain ageing

Bilkei-Gorzó

2012

Phil. Trans. R. Soc. B

121

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“…Aging is associated with a sort of paradox: a state of increased autoimmunity and inflammation coexistent with a state of immunodeficiency (Sardi et al 2011). Immunosenescence is a new concept that reflects the immunological changes associated with age.…”

Section: Immunosenescencementioning

confidence: 99%

Immune System Dysfunction in the Elderly

Fuentes

Alarcón

et al. 2017

An. Acad. Bras. Ciênc.

188

147

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Human aging is characterized by both physical and physiological frailty that profoundly affects the immune system. In this context aging is associated with declines in adaptive and innate immunity established as immunosenescence. Immunosenescence is a new concept that reflects the age-associated restructuring changes of innate and adaptive immune functions. Thus elderly individuals usually present chronic lowlevel inflammation, higher infection rates and chronic diseases. A study of alterations in the immune system during aging could provide a potentially useful biomarker for the evaluation of immune senescence treatment. The immune system is the result of the interplay between innate and adaptive immunity, yet the impact of aging on this function is unclear. In this article the function of the immune system during aging is explored.

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“…Similarly, the enrichment of metabolic pathways, organismal systems including nervous and immune system pathways, and common signaling pathways of the environmental information processing category is also expected and well-supported in the literature [54][55][56][57][58][59][60][61][62][63][64][65][66][67][68]. Interestingly, several genetic information processing pathways, including cell cycle regulation and DNA replication and repair, were found to be enriched.…”

Section: Snp-enriched Pathways and Associated Crosstalksmentioning

confidence: 72%

Characterizing Gene and Protein Crosstalks in Subjects at Risk of Developing Alzheimer’s Disease: A New Computational Approach

et al. 2017

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Alzheimer's disease (AD) is a major public health threat; however, despite decades of research, the disease mechanisms are not completely understood, and there is a significant dearth of predictive biomarkers. The availability of systems biology approaches has opened new avenues for understanding disease mechanisms at a pathway level. However, to the best of our knowledge, no prior study has characterized the nature of pathway crosstalks in AD, or examined their utility as biomarkers for diagnosis or prognosis. In this paper, we build the first computational crosstalk model of AD incorporating genetics, antecedent knowledge, and biomarkers from a national study to create a generic pathway crosstalk reference map and to characterize the nature of genetic and protein pathway crosstalks in mild cognitive impairment (MCI) subjects. We perform initial studies of the utility of incorporating these crosstalks as biomarkers for assessing the risk of MCI progression to AD dementia. Our analysis identified Single Nucleotide Polymorphism-enriched pathways representing six of the seven Kyoto Encyclopedia of Genes and Genomes pathway categories. Integrating pathway crosstalks as a predictor improved the accuracy by 11.7% compared to standard clinical parameters and apolipoprotein E ε4 status alone. Our findings highlight the importance of moving beyond discrete biomarkers to studying interactions among complex biological pathways.

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Alzheimer's disease, autoimmunity and inflammation. The good, the bad and the ugly

Cited by 161 publications

References 67 publications

The endocannabinoid system in normal and pathological brain ageing

The endocannabinoid system in normal and pathological brain ageing

Immune System Dysfunction in the Elderly

Characterizing Gene and Protein Crosstalks in Subjects at Risk of Developing Alzheimer’s Disease: A New Computational Approach

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