Inflammasome and α-synuclein in Parkinson's disease: A cross-sectional study

Chatterjee, Koustav; Roy, Akash; Banerjee, Rebecca; Choudhury, Supriyo; Mondal, Banashree; Halder, Saptak; Basu, Purba; Shubham, Shantanu; Dey, Sanjit; Kumar, Hrishikesh

doi:10.1016/j.jneuroim.2019.577089

Cited by 87 publications

(60 citation statements)

References 22 publications

(25 reference statements)

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“…Furthermore, the hepatic inhibition of NLRP3 was also shown to attenuate dopaminergic neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD, outlining the role of systemic activation of NLRP3 in PD. This is further supported by reports of elevated NLRP3, caspase-1 and IL-1β in the blood serum of PD patients and its correlation with α-synuclein [104,105].…”

Section: Neuroinflammatory Changes In Parkinson's Disease (Pd)supporting

confidence: 79%

Neurovascular Inflammaging in Health and Disease

Mészáros

Molnár

Nógrádi

et al. 2020

Cells

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Aging is characterized by a chronic low-grade sterile inflammation dubbed as inflammaging, which in part originates from accumulating cellular debris. These, acting as danger signals with many intrinsic factors such as cytokines, are sensed by a network of pattern recognition receptors and other cognate receptors, leading to the activation of inflammasomes. Due to the inflammasome activity-dependent increase in the levels of pro-inflammatory interleukins (IL-1β, IL-18), inflammation is initiated, resulting in tissue injury in various organs, the brain and the spinal cord included. Similarly, in age-related diseases of the central nervous system (CNS), inflammasome activation is a prominent moment, in which cells of the neurovascular unit occupy a significant position. In this review, we discuss the inflammatory changes in normal aging and summarize the current knowledge on the role of inflammasomes and contributing mechanisms in common CNS diseases, namely Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and stroke, all of which occur more frequently with aging.

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Section: Neuroinflammatory Changes In Parkinson's Disease (Pd)supporting

confidence: 79%

Neurovascular Inflammaging in Health and Disease

Mészáros

Molnár

Nógrádi

et al. 2020

Cells

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“…Rather than oligomers of α-Synuclein which only induce upregulation of IL-1β (Krashia et al, 2019), fibrillar α-Synuclein is able to elicit strong pro-inflammatory responses in a microglial cell line (Gustot et al, 2015;Hoffmann et al, 2016;Zhou et al, 2016). Fibrillar α-Synuclein can activate NLRP3 inflammasome which leads to the cleaving of pro-inflammatory cytokines, such as IL-1β and IL-18 (Zhou et al, 2016;Chatterjee et al, 2020;Haque et al, 2020). Also, using a rat model that overexpresses human α-Synuclein, Krashia et al found that α-Synuclein-induced inflammation precedes nigral degeneration, and administration of resolving D1, a potent lipid mediator that can resolve inflammation to promote restoration of tissue homeostasis, prevents neuronal dysfunction and motor deficits (Krashia et al, 2019).…”

Section: Proteostasis Of α-Synuclein and Inflammation Contribute To Ementioning

confidence: 99%

Proteostasis of α-Synuclein and Its Role in the Pathogenesis of Parkinson’s Disease

Han

Zheng

Wang

et al. 2020

Front. Cell. Neurosci.

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Aggregation of α-Synuclein, possibly caused by disturbance of proteostasis, has been identified as a common pathological feature of Parkinson's disease (PD). However, the initiating events of aggregation have not been fully illustrated, and this knowledge may be critical to understanding the disease mechanisms of PD. Proteostasis is essential in maintaining normal cellular metabolic functions, which regulate the synthesis, folding, trafficking, and degradation of proteins. The toxicity of the aggregating proteins is dramatically influenced by its physical and physiological status. Genetic mutations may also affect the metastable phase transition of proteins. In addition, neuroinflammation, as well as lipid metabolism and its interaction with α-Synuclein, are likely to contribute to the pathogenesis of PD. In this review article, we will highlight recent progress regarding α-Synuclein proteostasis in the context of PD. We will also discuss how the phase transition status of α-Synuclein could correlate with different functional consequences in PD.

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“…NLRP3, caspase-1, and IL-1β were increased in PD patients’ PBMCs and plasma when compared to age-matched healthy controls [ 115 , 116 , 117 ]. In addition, increased levels of IL-1b and IL-18 levels have been detected in the cerebrospinal fluid of PD patients [ 118 ].…”

Section: Immune Responses Induced By Dysfunctional Proteostasis Inmentioning

confidence: 99%

“…Increased plasma levels of α-SYN and IL-1β in PD patients have been shown to correlate with the motor severity in PD patients [ 115 ]. Moreover, the fibrillar form of α-SYN induced NLRP3–caspase-1 complex activation and the release of IL-1β in PBMCs, monocytes, microglia, and astrocytes [ 117 , 121 ]. Recently, the role of α-SYN and NLRP3 activation in astrocytes was demonstrated [ 121 ].…”

Section: Immune Responses Induced By Dysfunctional Proteostasis Inmentioning

confidence: 99%

Proteostasis Disturbances and Inflammation in Neurodegenerative Diseases

Sonninen

Goldsteins

Laham-Karam

et al. 2020

Cells

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Protein homeostasis (proteostasis) disturbances and inflammation are evident in normal aging and some age-related neurodegenerative diseases. While the proteostasis network maintains the integrity of intracellular and extracellular functional proteins, inflammation is a biological response to harmful stimuli. Cellular stress conditions can cause protein damage, thus exacerbating protein misfolding and leading to an eventual overload of the degradation system. The regulation of proteostasis network is particularly important in postmitotic neurons due to their limited regenerative capacity. Therefore, maintaining balanced protein synthesis, handling unfolding, refolding, and degrading misfolded proteins are essential to preserve all cellular functions in the central nervous sysytem. Failing proteostasis may trigger inflammatory responses in glial cells, and the consequent release of inflammatory mediators may lead to disturbances in proteostasis. Here, we review the mechanisms of proteostasis and inflammatory response, emphasizing their role in the pathological hallmarks of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Furthermore, we discuss the interplay between proteostatic stress and excessive immune response that activates inflammation and leads to dysfunctional proteostasis.

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Inflammasome and α-synuclein in Parkinson's disease: A cross-sectional study

Cited by 87 publications

References 22 publications

Neurovascular Inflammaging in Health and Disease

Neurovascular Inflammaging in Health and Disease

Proteostasis of α-Synuclein and Its Role in the Pathogenesis of Parkinson’s Disease

Proteostasis Disturbances and Inflammation in Neurodegenerative Diseases

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