Targeting the inflammasome in Parkinson’s disease

Su, Qi; Ng, Wei Lun; Goh, Suh Yee; Gulam, Muhammad Yaaseen; Wang, Lin‐Fa; Tan, Eng‐King; Ahn, Matae; Chao, Yin Xia

doi:10.3389/fnagi.2022.957705

Cited by 11 publications

(8 citation statements)

References 110 publications

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“…Although recently announced results indicated futility for slowing the progression of PD, an anti-inflammatory approach may require early treatment before LBP-related cell death to yield successful therapeutic effects [ 123 – 125 ]. Other clinical trials investigating anti-inflammatory agents are also still ongoing [ 126 , 127 ].…”

Section: Neuropathology Of Incidental Lbd (Ilbd)mentioning

confidence: 99%

Neuropathology of incidental Lewy body & prodromal Parkinson’s disease

Koeglsperger,

Rumpf,

Schließer

et al. 2023

Mol Neurodegeneration

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Background Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with a loss of dopaminergic (DA) neurons. Despite symptomatic therapies, there is currently no disease-modifying treatment to halt neuronal loss in PD. A major hurdle for developing and testing such curative therapies results from the fact that most DA neurons are already lost at the time of the clinical diagnosis, rendering them inaccessible to therapy. Understanding the early pathological changes that precede Lewy body pathology (LBP) and cell loss in PD will likely support the identification of novel diagnostic and therapeutic strategies and help to differentiate LBP-dependent and -independent alterations. Several previous studies identified such specific molecular and cellular changes that occur prior to the appearance of Lewy bodies (LBs) in DA neurons, but a concise map of such early disease events is currently missing. Methods Here, we conducted a literature review to identify and discuss the results of previous studies that investigated cases with incidental Lewy body disease (iLBD), a presumed pathological precursor of PD. Results Collectively, our review demonstrates numerous cellular and molecular neuropathological changes occurring prior to the appearance of LBs in DA neurons. Conclusions Our review provides the reader with a summary of early pathological events in PD that may support the identification of novel therapeutic and diagnostic targets and aid to the development of disease-modifying strategies in PD.

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Section: Neuropathology Of Incidental Lbd (Ilbd)mentioning

confidence: 99%

Neuropathology of incidental Lewy body & prodromal Parkinson’s disease

Koeglsperger,

Rumpf,

Schließer

et al. 2023

Mol Neurodegeneration

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“…Similar to AD, the key molecular mechanism of NLRP3 inflammasome initiation in PD is known to involve α-synuclein. α-Synuclein aggregation or fibrillation triggers delayed but potent activation of the NLRP3 inflammasome in mouse primary microglia [73].…”

Section: 12pdmentioning

confidence: 99%

Advances in the study of the role of extraoral bitter taste receptors

Zhen

Fang

et al. 2023

Preprint

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Taste is one of the basic senses of living organisms and can recognize sour, bitter, salty, sweet and umami tastes. Bitter taste receptor is a class of G protein-coupled receptors capable of sensing bitterness. Initially, bitter taste receptor was thought to be only found in the taste buds of the tongue, palate and throat. Recent research has shown that in addition to the oral cavity, the bitter taste receptor is also present in the intestinal tract, respiratory tract, urinary tract, vascular smooth muscle, nervous system, thyroid gland and other tissues and organs to regulate body homeostasis and resist disorders . In this review, we focus on the effects of the bitter taste receptor outside the oral cavity to lay the groundwork for future research.

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“…TNF-alpha (tumor necrosis factor alpha), IL-1, IL-2, IL-4, IL-6, epidermal growth factor (EGF), converting growth factor alpha (TGF-alpha), TGF-1, and TGF-2 have been recognized at elevated levels in nigrostriatal areas of the CNS and ventricular cerebrospinal fluid of Parkinson’s disease patients, supposedly emerging from activated microglia [ 37 , 39 , 40 ]. Neuronal damage may need prolonged exposure to proinflammatory cytokines such as IL-1, according to one theory [ 41 ]. On the cell bodies and processes of nigrostriatal neurons exist receptors for proinflammatory cytokines, including TNF-alpha, which probably renders the neurons that are vulnerable to the devastating impacts of cytokines produced by stimulated microglia [ 36 ].…”

Section: Parkinson’s Disease and Microglia: A Look At Their Involvementmentioning

confidence: 99%

“…In response to cytokines that assault nigrostriatal neurons, microglial activity might potentially harm and kill neurons through additional methods [ 40 ]. Postmortem analysis of Parkinson’s disease brains has shown indications of oxidative stress [ 40 , 41 , 42 ]. Activated microglia produce nitric oxide (NO) and superoxide, which may mix to create peroxynitrite, a highly reactive and toxic oxidant that damages and kills cells by interacting with DNA, proteins, and lipids [ 40 , 41 , 42 ].…”

Section: Parkinson’s Disease and Microglia: A Look At Their Involvementmentioning

confidence: 99%

“…Postmortem analysis of Parkinson’s disease brains has shown indications of oxidative stress [ 40 , 41 , 42 ]. Activated microglia produce nitric oxide (NO) and superoxide, which may mix to create peroxynitrite, a highly reactive and toxic oxidant that damages and kills cells by interacting with DNA, proteins, and lipids [ 40 , 41 , 42 ]. Furthermore, NO generated by active microglia may traverse cell membranes and enter dopaminergic neurons in order to communicate with superoxide generated inside the neuron and cause oxidative damage that inevitably results in neuronal death [ 43 ].…”

Section: Parkinson’s Disease and Microglia: A Look At Their Involvementmentioning

confidence: 99%

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Infectious Microorganisms Seen as Etiologic Agents in Parkinson’s Disease

Stroe

Jurja

Mehedinți

et al. 2023

Life

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Infections represent a possible risk factor for parkinsonism and Parkinson’s disease (PD) based on information from epidemiology and fundamental science. The risk is unclear for the majority of agents. Moreover, the latency between infection and PD seems to be very varied and often lengthy. In this review, the evidence supporting the potential involvement of infectious microorganisms in the development of Parkinson’s disease is examined. Consequently, it is crucial to determine the cause and give additional treatment accordingly. Infection is an intriguing suggestion regarding the cause of Parkinson’s disease. These findings demonstrate that persistent infection with viral and bacterial microorganisms might be a cause of Parkinson’s disease. As an initiating factor, infection may generate a spectrum of gut microbiota dysbiosis, engagement of glial tissues, neuroinflammation, and alpha-synuclein accumulation, all of which may trigger and worsen the onset in Parkinson’s disease also contribute to its progression. Still uncertain is the primary etiology of PD with infection. The possible pathophysiology of PD infection remains a matter of debate. Furthermore, additional study is required to determine if PD patients develop the disease due to infectious microorganisms or solely since they are more sensitive to infectious causes.

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Targeting the inflammasome in Parkinson’s disease

Cited by 11 publications

References 110 publications

Neuropathology of incidental Lewy body & prodromal Parkinson’s disease

Neuropathology of incidental Lewy body & prodromal Parkinson’s disease

Advances in the study of the role of extraoral bitter taste receptors

Infectious Microorganisms Seen as Etiologic Agents in Parkinson’s Disease

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