Pyroptosis in neurodegenerative diseases: from bench to bedside

Wu, Kejia; Wang, W.; Cheng, Qi; Li, Hao; Yan, W. M.; Zhou, Fu-zhen; Zhang, Ruijie

doi:10.1007/s10565-023-09820-x

Cited by 12 publications

(2 citation statements)

References 192 publications

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“…In recent research, there has been substantial evidence supporting the involvement of microglial pro-inflammatory signaling in the development of PD ( 320 , 321 ). These studies specifically emphasize the importance of activating the microglial NLRP3 inflammasome in the onset of PD ( 322 , 323 ). Furthermore, a recent investigation has unveiled intriguing insights into how α-synuclein (α-syn) is regulated within microglia, pinpointing Fyn kinase as the key regulator in this process ( 324 , 325 ).…”

Section: Navigating the Course Of Neuroinflammation And Microglial Ac...mentioning

confidence: 99%

Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression

Fornari Laurindo,

Aparecido Dias,

Cressoni Araújo

et al. 2024

Front. Immunol.

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The increasing life expectancy has led to a higher incidence of age-related neurodegenerative conditions. Within this framework, neuroinflammation emerges as a significant contributing factor. It involves the activation of microglia and astrocytes, leading to the release of pro-inflammatory cytokines and chemokines and the infiltration of peripheral leukocytes into the central nervous system (CNS). These instances result in neuronal damage and neurodegeneration through activated nucleotide-binding domain and leucine-rich repeat containing (NLR) family pyrin domain containing protein 3 (NLRP3) and nuclear factor kappa B (NF-kB) pathways and decreased nuclear factor erythroid 2-related factor 2 (Nrf2) activity. Due to limited effectiveness regarding the inhibition of neuroinflammatory targets using conventional drugs, there is challenging growth in the search for innovative therapies for alleviating neuroinflammation in CNS diseases or even before their onset. Our results indicate that interventions focusing on Interleukin-Driven Immunomodulation, Chemokine (CXC) Receptor Signaling and Expression, Cold Exposure, and Fibrin-Targeted strategies significantly promise to mitigate neuroinflammatory processes. These approaches demonstrate potential anti-neuroinflammatory effects, addressing conditions such as Multiple Sclerosis, Experimental autoimmune encephalomyelitis, Parkinson’s Disease, and Alzheimer’s Disease. While the findings are promising, immunomodulatory therapies often face limitations due to Immune-Related Adverse Events. Therefore, the conduction of randomized clinical trials in this matter is mandatory, and will pave the way for a promising future in the development of new medicines with specific therapeutic targets.

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Section: Navigating the Course Of Neuroinflammation And Microglial Ac...mentioning

confidence: 99%

Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression

Fornari Laurindo,

Aparecido Dias,

Cressoni Araújo

et al. 2024

Front. Immunol.

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“…In turn, this activation leads to the maturation of pro-IL-1β and pro-IL-18 into active inflammatory cytokines [46]. For this reason, once activated, inflammasomes promote an innate immune response against harmful agents through IL-1β and IL-18 but also induce pyroptosis, a form of cell death that provides additional inflammatory stimuli [47]. In the context of neurodegenerative diseases, the most investigated inflammasome is the nucleotide-binding domain (NOD), leucine-rich repeat (LRR), and pyrin domain-containing protein-3 (NLRP3) inflammasome.…”

Section: Scfasmentioning

confidence: 99%

Gut–Brain Axis: Focus on Sex Differences in Neuroinflammation

Caldarelli,

Rio,

Marrone

et al. 2024

IJMS

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In recent years, there has been a growing interest in the concept of the “gut–brain axis”. In addition to well-studied diseases associated with an imbalance in gut microbiota, such as cancer, chronic inflammation, and cardiovascular diseases, research is now exploring the potential role of gut microbial dysbiosis in the onset and development of brain-related diseases. When the function of the intestinal barrier is altered by dysbiosis, the aberrant immune system response interacts with the nervous system, leading to a state of “neuroinflammation”. The gut microbiota–brain axis is mediated by inflammatory and immunological mechanisms, neurotransmitters, and neuroendocrine pathways. This narrative review aims to illustrate the molecular basis of neuroinflammation and elaborate on the concept of the gut–brain axis by virtue of analyzing the various metabolites produced by the gut microbiome and how they might impact the nervous system. Additionally, the current review will highlight how sex influences these molecular mechanisms. In fact, sex hormones impact the brain–gut microbiota axis at different levels, such as the central nervous system, the enteric nervous one, and enteroendocrine cells. A deeper understanding of the gut–brain axis in human health and disease is crucial to guide diagnoses, treatments, and preventive interventions.

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