Update of inflammasome activation in microglia/macrophage in aging and aging‐related disease

Hu, Mengyan; Lin, Yinyao; Zhang, Bingjun; Lu, Danli; Lu, Zhengqi; Cai, Wei

doi:10.1111/cns.13262

Cited by 46 publications

(35 citation statements)

References 91 publications

(192 reference statements)

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“…The concept of "inflamm-aging, " the low-grade chronic inflammatory state that accompanies aging, is a recent topic of interest (55). During aging, inflammasome activation can be triggered by local microenvironment changes associated with aging microglia (56). For example, aging microglia exhibit altered cytokine production, making microglial cells more susceptible to adopting a pro-inflammatory state that also primes the cells for inflammasome activation (56,57).…”

Section: Nlrp3 Inflammasome In Normal Agingmentioning

confidence: 99%

“…During aging, inflammasome activation can be triggered by local microenvironment changes associated with aging microglia (56). For example, aging microglia exhibit altered cytokine production, making microglial cells more susceptible to adopting a pro-inflammatory state that also primes the cells for inflammasome activation (56,57). Aging microglial cells also have an increased accumulation of lipofuschin that has been associated with increased oxidative stress, which may cause microglia to lose their neuroprotective potential and contribute to age-related pathology (58,59).…”

Section: Nlrp3 Inflammasome In Normal Agingmentioning

confidence: 99%

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The Role of Microglia and the Nlrp3 Inflammasome in Alzheimer's Disease

2020

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Alzheimer's disease (AD) is the most prevalent form of late-onset dementia. AD affects the health of millions of people in the United States and worldwide. Currently, there are no approved therapies that can halt or reverse the clinical progression of AD. Traditionally, AD is characterized first by the appearance of amyloid-β (Aβ) plaques followed by the formation of intraneuronal neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau (p-tau). These lesions are linked to synapse loss and eventual cognitive impairment. Additionally, microgliosis is consistently found in regions of the brain with AD pathology. The role of microglia in AD onset and progression remains unclear. Several recent reports indicate that the assembly of the multi-protein complex known as the NOD, LRR, and pyrin-domain containing 3 (Nlrp3) inflammasome by microglia results in apoptosis spec-like protein containing a CARD (Asc) spec formation, which then nucleates new Aβ plaques, thus amplifying Aβ-associated pathology. NFTs can also activate the Nlrp3 inflammasome leading to enhanced tau-associated pathology. Here, we will review the role of microglia and the activation of the inflammasome in the innate immune response to AD.

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Section: Nlrp3 Inflammasome In Normal Agingmentioning

confidence: 99%

Section: Nlrp3 Inflammasome In Normal Agingmentioning

confidence: 99%

The Role of Microglia and the Nlrp3 Inflammasome in Alzheimer's Disease

2020

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“…The immune imbalance in aging occurs due to various alterations in cellular behavior and phenotype, which cause functional deficiencies in immune cells ( 3 ). For example, this context induces polarization of macrophages towards an inflammatory phenotype characterized by strong activation of the inflammasome ( 234 ). Thus, these events could induce IL1β and TNFα release, changes in the chemoattraction of neutrophils mediated by the reduction of the intercellular adhesion molecule 1 (ICAM-1) expression, and the aberrant activation of the phosphoinositide lipid kinase-3 (PI3K) ( 235 ).…”

Section: Aging Epigenetic and Immuno-inflammatory Imbalancementioning

confidence: 99%

The Challenge by Multiple Environmental and Biological Factors Induce Inflammation in Aging: Their Role in the Promotion of Chronic Disease

et al. 2020

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The aging process is driven by multiple mechanisms that lead to changes in energy production, oxidative stress, homeostatic dysregulation and eventually to loss of functionality and increased disease susceptibility. Most aged individuals develop chronic low-grade inflammation, which is an important risk factor for morbidity, physical and cognitive impairment, frailty, and death. At any age, chronic inflammatory diseases are major causes of morbimortality, affecting up to 5–8% of the population of industrialized countries. Several environmental factors can play an important role for modifying the inflammatory state. Genetics accounts for only a small fraction of chronic-inflammatory diseases, whereas environmental factors appear to participate, either with a causative or a promotional role in 50% to 75% of patients. Several of those changes depend on epigenetic changes that will further modify the individual response to additional stimuli. The interaction between inflammation and the environment offers important insights on aging and health. These conditions, often depending on the individual’s sex, appear to lead to decreased longevity and physical and cognitive decline. In addition to biological factors, the environment is also involved in the generation of psychological and social context leading to stress. Poor psychological environments and other sources of stress also result in increased inflammation. However, the mechanisms underlying the role of environmental and psychosocial factors and nutrition on the regulation of inflammation, and how the response elicited for those factors interact among them, are poorly understood. Whereas certain deleterious environmental factors result in the generation of oxidative stress driven by an increased production of reactive oxygen and nitrogen species, endoplasmic reticulum stress, and inflammation, other factors, including nutrition (polyunsaturated fatty acids) and behavioral factors (exercise) confer protection against inflammation, oxidative and endoplasmic reticulum stress, and thus ameliorate their deleterious effect. Here, we discuss processes and mechanisms of inflammation associated with environmental factors and behavior, their links to sex and gender, and their overall impact on aging.

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“…Neuroinflammation is closely involved in the pathophysiology of VCID 50 . Inflammatory‐related microglia causes cognitive impairment by activating receptor for advanced glycation end products (RAGE), which is present on both microglia and neurons.…”

Section: Overview Of Vascular Cognitive Impairment and Dementia (Vcid)mentioning

confidence: 99%

Regulatory microRNAs and vascular cognitive impairment and dementia

et al. 2020

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Vascular cognitive impairment and dementia (VCID) is currently the second most common type of dementia just after Alzheimer's disease (AD). 1 In 2015, approximately 47.5 million people were affected by dementia, which is expected to increase to 75.6 million by 2030. The annual global social cost for VCID and vascular dementia (VaD) is $604 billion, accounting for 1.0% of the global gross domestic product. 2 Vascular cognitive impairment and dementia occurs when cerebral blood flow is compromised. It is a comprehensive brain disorder that comprises mild cognitive impairment (MCI), VaD, and mixed dementia, such as mixed vascular and AD-type cognitive impairment. 3 VCID presents a significant decline in cognitive function due to cerebral vascular damage, including clinical stroke, asymptomatic infarcts and microinfarcts, leukoaraiosis, cerebral amyloid angiopathy (CAA), 4 transient ischemic attack (TIA), and micro hemorrhage. 5 Diagnosis is further defined according to whether there is a causal relationship between cognitive impairment syndrome and vascular disease. 6,7 Up to now, treatment for VCID is still limited to relief and therapy of symptoms. 8 For example, Donepezil was found to enhance the cognitive ability of VaD patients. 3 Administration of Galantamine is beneficial for patients with mixed AD and VaD. 9 Non-coding RNAs, especially miRs, are one of the many biological factors that cause functional changes during VCID. Because of

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Update of inflammasome activation in microglia/macrophage in aging and aging‐related disease

Cited by 46 publications

References 91 publications

The Role of Microglia and the Nlrp3 Inflammasome in Alzheimer's Disease

The Role of Microglia and the Nlrp3 Inflammasome in Alzheimer's Disease

The Challenge by Multiple Environmental and Biological Factors Induce Inflammation in Aging: Their Role in the Promotion of Chronic Disease

Regulatory microRNAs and vascular cognitive impairment and dementia

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