Chronic cerebral hypoperfusion activates AIM2 and NLRP3 inflammasome

Matsuyama, Hirofumi; Shindo, Akihiro; Shimada, Takuya; Yata, Kenichiro; Wakita, Hideaki; Takahashi, Ryōsuke; Tomimoto, Hidekazu

doi:10.1016/j.brainres.2020.146779

Cited by 29 publications

(22 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This review illustrates the mechanisms of inflammasome-mediated neuroinflammation under CCH in VCI. By providing direct evidence of inflammasome activation in VCI animal models and patients, we suggest that the critical involvement of the inflammasome signaling pathway in the pathogenesis of VCI may be mediated through CCH [ 64 – 66 , 71 , 118 , 119 , 193 , 317 ]. Most importantly, inflammasome-mediated inflammatory mechanisms are early events that persist till the late stage of VCI; this sheds light on the inflammasome signaling pathway as a potential therapeutic target [ 64 – 66 , 71 , 118 , 119 , 193 , 317 ].…”

Section: Discussionmentioning

confidence: 99%

“…By providing direct evidence of inflammasome activation in VCI animal models and patients, we suggest that the critical involvement of the inflammasome signaling pathway in the pathogenesis of VCI may be mediated through CCH [ 64 – 66 , 71 , 118 , 119 , 193 , 317 ]. Most importantly, inflammasome-mediated inflammatory mechanisms are early events that persist till the late stage of VCI; this sheds light on the inflammasome signaling pathway as a potential therapeutic target [ 64 – 66 , 71 , 118 , 119 , 193 , 317 ]. By reducing inflammasome activity levels, we can attenuate its influence on various pathogenic cellular mechanisms and structural damage observed during the disease progression of VCI [ 119 , 291 ].…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have indicated a close association of inflammasome activity with the formation of WMLs that often occur together with activated microglia [ 77 , 203 , 317 ]. As mentioned, activated microglia release numerous inflammatory mediators that contribute to demyelination, including IL-1β and IL-18 that are produced during inflammasome activation.…”

Section: Inflammasome Signaling Pathway: Linking Il-1 To Vcimentioning

confidence: 99%

“…In addition to the presence of inflammasome-mediated proinflammatory cytokine production, immunostaining of inflammasome receptors, NLRP3 and AIM2, was greater in white matter lesions of patients with cerebral infarction [ 317 ]. Together these studies provide evidence of inflammasome activation in a severe state of VCI, highlighting the prominence of inflammasome signaling in the disease progression of VCI.…”

Section: Evidence Of Inflammasome Activity In Vci In Humansmentioning

confidence: 99%

See 3 more Smart Citations

The role of inflammasomes in vascular cognitive impairment

Poh

Sim

et al. 2022

Mol Neurodegeneration

View full text Add to dashboard Cite

There is an increasing prevalence of Vascular Cognitive Impairment (VCI) worldwide, and several studies have suggested that Chronic Cerebral Hypoperfusion (CCH) plays a critical role in disease onset and progression. However, there is a limited understanding of the underlying pathophysiology of VCI, especially in relation to CCH. Neuroinflammation is a significant contributor in the progression of VCI as increased systemic levels of the proinflammatory cytokine interleukin-1β (IL-1β) has been extensively reported in VCI patients. Recently it has been established that CCH can activate the inflammasome signaling pathways, involving NLRP3 and AIM2 inflammasomes that critically regulate IL-1β production. Given that neuroinflammation is an early event in VCI, it is important that we understand its molecular and cellular mechanisms to enable development of disease-modifying treatments to reduce the structural brain damage and cognitive deficits that are observed clinically in the elderly. Hence, this review aims to provide a comprehensive insight into the molecular and cellular mechanisms involved in the pathogenesis of CCH-induced inflammasome signaling in VCI.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Inflammasome Signaling Pathway: Linking Il-1 To Vcimentioning

confidence: 99%

Section: Evidence Of Inflammasome Activity In Vci In Humansmentioning

confidence: 99%

See 2 more Smart Citations

The role of inflammasomes in vascular cognitive impairment

Poh

Sim

et al. 2022

Mol Neurodegeneration

View full text Add to dashboard Cite

show abstract

“…Chronic cerebral hypoperfusion, which is a state of chronic cerebral blood flow reduction, is associated with some cerebrovascular and neurodegenerative diseases, such as Alzheimer's disease (AD) and carotid artery stenosis (Hainsworth and Markus, 2008;Arsava et al, 2018;Choi et al, 2019;Shang et al, 2019). CCH is reported to increase the levels of NLRP3, caspase-1, and IL-1β in the hippocampus and thalamus of AD mice (Shang et al, 2019;Matsuyama et al, 2020). However, the effects of autophagy on the NLRP3 inflammasome in CCH has not been studied.…”

Section: The Effects Of Autophagy On the Nlrp3 Inflammasome In Chronic Cerebral Hypoperfusionmentioning

confidence: 99%

The Role of the Effects of Autophagy on NLRP3 Inflammasome in Inflammatory Nervous System Diseases

Zhao

Wang

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Autophagy is a stable self-sustaining process in eukaryotic cells. In this process, pathogens, abnormal proteins, and organelles are encapsulated by a bilayer membrane to form autophagosomes, which are then transferred to lysosomes for degradation. Autophagy is involved in many physiological and pathological processes. Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, containing NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and pro-caspase-1, can activate caspase-1 to induce pyroptosis and lead to the maturation and secretion of interleukin-1 β (IL-1 β) and IL-18. NLRP3 inflammasome is related to many diseases. In recent years, autophagy has been reported to play a vital role by regulating the NLRP3 inflammasome in inflammatory nervous system diseases. However, the related mechanisms are not completely clarified. In this review, we sum up recent research about the role of the effects of autophagy on NLRP3 inflammasome in Alzheimer’s disease, chronic cerebral hypoperfusion, Parkinson’s disease, depression, cerebral ischemia/reperfusion injury, early brain injury after subarachnoid hemorrhage, and experimental autoimmune encephalomyelitis and analyzed the related mechanism to provide theoretical reference for the future research of inflammatory neurological diseases.

show abstract

Hypertension and hyperhomocysteinemia as modifiable risk factors for Alzheimer's disease and dementia: New evidence, potential therapeutic strategies, and biomarkers

Carey

Fossati

2022

Alzheimer's & Dementia

View full text Add to dashboard Cite

This review summarizes recent evidence on how mid-life hypertension, hyperhomocysteinemia (HHcy) and blood pressure variability, as well as late-life hypotension, exacerbate Alzheimer's disease (AD) and dementia risk. Intriguingly, HHcy also increases the risk for hypertension, revealing the importance of understanding the relationship between comorbid cardiovascular risk factors. Hypertension-induced dementia presents more evidently in women, highlighting the relevance of sex differences in the impact of cardiovascular risk. We summarize each major antihypertensive drug class's effects on cognitive impairment and AD pathology, revealing how carbonic anhydrase inhibitors, diuretics modulating cerebral blood flow, have recently gained preclinical evidence as promising treatment against AD. We also report novel vascular biomarkers for AD and dementia risk, highlighting those associated with hypertension and HHcy. Importantly, we propose that future studies should consider hypertension and HHcy as potential contributors to cognitive impairment, and that uncovering the underlying molecular mechanisms and biomarkers would aid in the identification of preventive strategies.

show abstract

Chronic cerebral hypoperfusion activates AIM2 and NLRP3 inflammasome

Cited by 29 publications

References 22 publications

The role of inflammasomes in vascular cognitive impairment

The role of inflammasomes in vascular cognitive impairment

The Role of the Effects of Autophagy on NLRP3 Inflammasome in Inflammatory Nervous System Diseases

Hypertension and hyperhomocysteinemia as modifiable risk factors for Alzheimer's disease and dementia: New evidence, potential therapeutic strategies, and biomarkers

Contact Info

Product

Resources

About