Role of Microgliosis and NLRP3 Inflammasome in Parkinson’s Disease Pathogenesis and Therapy

Araújo, F.; Cuenca‐Bermejo, Lorena; Fernández-Villalba, Emiliano; Costa, Sílvia Lima; Silva, Victor Diógenes A.; Herrero, M.T.

doi:10.1007/s10571-020-01027-6

Cited by 40 publications

(36 citation statements)

References 210 publications

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“…These activated microglia assume an amoeboid morphology, coupled with increased phagocytic capacity. They are also highly reactive and are associated with expression of inflammatory molecules, such as pro-inflammatory mediators and reactive species, in addition to receptors for antigen recognition such as TLR2 ( 2 ). Their physiological cellular processes are also thought to be disrupted as a result, further contributing to disease pathogenesis.…”

Section: Microglia and Their Role In Parkinson's Diseasementioning

confidence: 99%

“…In PD, excess and/or mutant α-syn aggregates form fibrils. These neurotoxic fibrils act as an endogenous DAMP causing activation of microglia via TLR2 ( 2 , 94 ) resulting in the activation of NF-κB and MAPK pathways and the production and release of pro-inflammatory mediators such as TNF-α, IL-6, CCL5, and IL-1β ( 2 , 36 ). Interestingly, microglia activation in response to α-syn has been demonstrated to be mutant specific ( 94 ) ( Table 2 ).…”

Section: Microglia and Their Role In Parkinson's Diseasementioning

confidence: 99%

“…Mitochondrial dysfunction can result in the release of numerous pro-inflammatory factors such as mitochondrial DNA, RNA, ATP, and cytochrome c ( 110 ). The presence of ROS and DNA from damaged mitochondria can act as danger signals for activation of the NLRP3 inflammasome which is involved in neuroinflammation in PD ( 2 , 155 , 156 ). Mitochondrial dysfunction has been shown to over-activate the NLRP3 inflammasome in microglia resulting in dopaminergic neuron cell death ( 157 ).…”

Section: An Emerging Role For the Peripheral Immune System In Parkinson's Diseasementioning

confidence: 99%

“…Parkinson's disease (PD) is the second most common neurodegenerative disease affecting 1–2% of the population over the age of 65 ( 1 ) and it is estimated that the number of cases will exceed 12 million individuals in 2040 ( 2 ). PD is characterised by the degeneration of dopamine neurons in the substantia nigra (SN) of the midbrain, with concomitant loss of their axons that project to the striatum along the nigrostriatal pathway.…”

Section: Introductionmentioning

confidence: 99%

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The Pathogenesis of Parkinson's Disease: A Complex Interplay Between Astrocytes, Microglia, and T Lymphocytes?

et al. 2021

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Parkinson's disease (PD), the second most common neurodegenerative disease, is characterised by the motor symptoms of bradykinesia, rigidity and resting tremor and non-motor symptoms of sleep disturbances, constipation, and depression. Pathological hallmarks include neuroinflammation, degeneration of dopaminergic neurons in the substantia nigra pars compacta, and accumulation of misfolded α-synuclein proteins as intra-cytoplasmic Lewy bodies and neurites. Microglia and astrocytes are essential to maintaining homeostasis within the central nervous system (CNS), including providing protection through the process of gliosis. However, dysregulation of glial cells results in disruption of homeostasis leading to a chronic pro-inflammatory, deleterious environment, implicated in numerous CNS diseases. Recent evidence has demonstrated a role for peripheral immune cells, in particular T lymphocytes in the pathogenesis of PD. These cells infiltrate the CNS, and accumulate in the substantia nigra, where they secrete pro-inflammatory cytokines, stimulate surrounding immune cells, and induce dopaminergic neuronal cell death. Indeed, a greater understanding of the integrated network of communication that exists between glial cells and peripheral immune cells may increase our understanding of disease pathogenesis and hence provide novel therapeutic approaches.

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Section: Microglia and Their Role In Parkinson's Diseasementioning

confidence: 99%

Section: Microglia and Their Role In Parkinson's Diseasementioning

confidence: 99%

Section: An Emerging Role For the Peripheral Immune System In Parkinson's Diseasementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Pathogenesis of Parkinson's Disease: A Complex Interplay Between Astrocytes, Microglia, and T Lymphocytes?

et al. 2021

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“…Microgliosis is the reaction of CNS microglial cells to pathogenic insults and their shift from a resting to the active state [ 440 ]. Since the first study demonstrating microgliosis in PD brains [ 25 ], a plethora of reports highlights an important role of activated microglia in disease pathogenesis in both humans and animal models (reviewed in [ 441 , 442 , 443 , 444 , 445 ]). Microglial activation has been observed in PD brains by in vivo positron emission tomography (PET) imaging studies [ 446 , 447 , 448 ], suggesting that microgliosis is an early event that perpetuates during the disease progression.…”

Section: Glia In the Cns: Scavengers Of Extracellular Asynmentioning

confidence: 99%

Neurons and Glia Interplay in α-Synucleinopathies

Mavroeidi

Xilouri

2021

IJMS

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Accumulation of the neuronal presynaptic protein alpha-synuclein within proteinaceous inclusions represents the key histophathological hallmark of a spectrum of neurodegenerative disorders, referred to by the umbrella term a-synucleinopathies. Even though alpha-synuclein is expressed predominantly in neurons, pathological aggregates of the protein are also found in the glial cells of the brain. In Parkinson’s disease and dementia with Lewy bodies, alpha-synuclein accumulates mainly in neurons forming the Lewy bodies and Lewy neurites, whereas in multiple system atrophy, the protein aggregates mostly in the glial cytoplasmic inclusions within oligodendrocytes. In addition, astrogliosis and microgliosis are found in the synucleinopathy brains, whereas both astrocytes and microglia internalize alpha-synuclein and contribute to the spread of pathology. The mechanisms underlying the pathological accumulation of alpha-synuclein in glial cells that under physiological conditions express low to non-detectable levels of the protein are an area of intense research. Undoubtedly, the presence of aggregated alpha-synuclein can disrupt glial function in general and can contribute to neurodegeneration through numerous pathways. Herein, we summarize the current knowledge on the role of alpha-synuclein in both neurons and glia, highlighting the contribution of the neuron-glia connectome in the disease initiation and progression, which may represent potential therapeutic target for a-synucleinopathies.

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Role of NLRP3 inflammasome-mediated neuronal pyroptosis and neuroinflammation in neurodegenerative diseases

Han,

Liu,

Jin

et al. 2023

Inflamm. Res.

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Role of Microgliosis and NLRP3 Inflammasome in Parkinson’s Disease Pathogenesis and Therapy

Cited by 40 publications

References 210 publications

The Pathogenesis of Parkinson's Disease: A Complex Interplay Between Astrocytes, Microglia, and T Lymphocytes?

The Pathogenesis of Parkinson's Disease: A Complex Interplay Between Astrocytes, Microglia, and T Lymphocytes?

Neurons and Glia Interplay in α-Synucleinopathies

Role of NLRP3 inflammasome-mediated neuronal pyroptosis and neuroinflammation in neurodegenerative diseases

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