The role of microglial autophagy in Parkinson’s disease

Zhu, Rui; Luo, Yuyi; Li, Shangang; Wang, Zhengbo

doi:10.3389/fnagi.2022.1039780

Cited by 13 publications

(3 citation statements)

References 90 publications

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“…Furthermore, microglia perform autophagy process to engulf neuron-released αsynuclein for degradation. Autophagy dysfunction and αsynuclein accumulation widely contribute to PD development and pathophysiology [36]. Markedly, "RAGE", "autophagy" and "α-synuclein" were among the top keywords used in the HMGB1-PD research.…”

Section: Discussionmentioning

confidence: 99%

High-Mobility Group Box 1 (HMGB1) Protein in Parkinson's Disease Research: A 10-Year Bibliometric Analysis

Razali¹,

Mohamed²

2023

J. Integr. Neurosci.

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Background: Parkinson's disease (PD), the most prevalent motoric neurodegenerative disease, has been intensively studied to better comprehend its complicated pathogenesis. Chronic neuroinflammation is a major factor contributing to the development of PD. Reportedly, high-mobility group box 1 (HMGB1) protein is capable of mediating neuroinflammatory response. In this regard, knowledge mapping of the research linking HMGB1 to PD is necessary. Objective: Herein, we perform a dynamic and longitudinal bibliometric analysis to explore the hotspots and current trends of HMGB1-related PD publications during the past decade. Methods: All PD publications focusing on HMGB1 protein were retrieved from the PubMed database using the search terms "Parkinson's disease" and "hmgb1". Using filters, only English articles published between 2011 and 2022 were selected. The Bibliometrix and Biblioshiny packages from R software were used to conduct the bibliometric analysis. Results: The filtered search identified 47 articles (34 original articles and 13 review articles), published between 2011 and 2022. There was an increase trend in the number of articles published, with an annual growth rate of 19.35 percent. In terms of research and scientific collaboration in this field, the United States is in the lead, followed by China, Malaysia, and Australia. Compared to other countries, the United States and China had the highest level of collaboration in this research area. Neuroinflammation, microglia, and receptor for advanced glycation end-products (RAGE) represent the top three frontiers and hotspots for HMGB1-related PD research. According to the thematic evolution analysis, over the last decade, PD, HMGB1 and microglia were addressed individually, however, since 2017, these topics were frequently discussed within the same cluster: neuroinflammation. Furthermore, PD, HMGB1, and neuroinflammation domains co-occurred in majority of the research discussion. Conclusions: The link between HMGB1 and PD was realized a decade ago and becomes increasingly important over time. Our findings can aid scholars in comprehending the global context of HMGB1/PD relationship and provide significant insights for future PD research.

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Section: Discussionmentioning

confidence: 99%

High-Mobility Group Box 1 (HMGB1) Protein in Parkinson's Disease Research: A 10-Year Bibliometric Analysis

Razali¹,

Mohamed²

2023

J. Integr. Neurosci.

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“…Multiple pro- and anti-inflammatory neuroimmune signaling pathways have been demonstrated to coordinately regulate the status of microglia activation [ 6 , 7 ]. Abnormal microglia activation (neuroinflammation) has been implicated as a major risk factor contributing to the pathogenesis of multiple neurodegenerative diseases including Alzheimer’s diseases (ADs) [ 8 , 9 ], Parkinson’s diseases (PDs) [ 10 , 11 ], amyotrophic lateral sclerosis (ALS) [ 12 ], as well as recently SUDs [ 13 , 14 ]. NLRP3 inflammasome belongs to the superfamily of pattern-recognition receptors (PRRs) recognizing pathogen-associated molecular patterns.…”

Section: Introductionmentioning

confidence: 99%

Microglia NLRP3 Inflammasome and Neuroimmune Signaling in Substance Use Disorders

et al. 2023

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During the last decade, substance use disorders (SUDs) have been increasingly recognized as neuroinflammation-related brain diseases. Various types of abused drugs (cocaine, methamphetamine, alcohol, opiate-like drugs, marijuana, etc.) can modulate the activation status of microglia and neuroinflammation levels which are involved in the pathogenesis of SUDs. Several neuroimmune signaling pathways, including TLR/NF-кB, reactive oxygen species, mitochondria dysfunction, as well as autophagy defection, etc., have been implicated in promoting SUDs. Recently, inflammasome-mediated signaling has been identified as playing critical roles in the microglia activation induced by abused drugs. Among the family of inflammasomes, NOD-, LRR-, and pyrin-domain-containing protein 3 (NLRP3) serves the primary research target due to its abundant expression in microglia. NLRP3 has the capability of integrating multiple external and internal inputs and coordinately determining the intensity of microglia activation under various pathological conditions. Here, we summarize the effects of abused drugs on NLRP3 inflammasomes, as well as others, if any. The research on this topic is still at an infant stage; however, the readily available findings suggest that NLRP3 inflammasome could be a common downstream effector stimulated by various types of abused drugs and play critical roles in determining abused-drug-mediated biological effects through enhancing glia–neuron communications. NLRP3 inflammasome might serve as a novel target for ameliorating the development of SUDs.

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“…Autophagy dysfunction has been closely related with pathogenesis of many neurodegenerative diseases [14]. In this regard, it is important to note that autophagy can also serve as controlling mechanism of the metabolic and immune status of microglia and thus balance neuroinflammatory response [14][15][16]. For instance, ATG7 gene-deficient microglial cells, show transcriptional and functional similarity to the functionally incompetent microglia from the aged wild-type mice [17].…”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicles promote autophagy in human microglia through lipid raft-dependent mechanisms

Romenskaja

Jonavičė

Pivoriūnas

2023

Preprint

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Autophagy dysfunction has been closely related with pathogenesis of many neurodegenerative diseases and therefore represents a potential therapeutic target. Extracellular vesicles (EVs) may act as a potent anti-inflammatory agents and also modulators of autophagy in target cells. However, the molecular mechanisms by which EVs modulate autophagy flux in human microglia remain largely unexplored. In the present study we investigated the effects of EVs derived from human oral mucosa stem cells on the autophagy in human microglia. We demonstrate that EVs promoted autophagy and autophagic flux in human microglia and that this process was dependent on the integrity of lipid rafts. LPS also activated autophagy, but combined treatment with EVs and LPS suppressed autophagy response indicating interference between these signalling pathways. Blockage of Toll-like receptor 4 (TLR4) with anti-TLR4 antibody suppressed EV-induced autophagy. Furthermore, blockage of EV- asscoiated HSP70 chaperone which is one of the endogenous ligands of the TLR4 also suppressed EV- induced lipid raft formation and autophagy. Pre-treatment of microglia with selective inhibitor of αvβ3/αvβ5 integrins cilengitide inhibited EV-induced autophagy. Finally, blockage of purinergic P2X4 receptor (P2X4R) with selective inhibitor 5-BDBD also suppressed of EV-induced autophagy. In conclusion, we demonstrate that EVs activate autophagy in human microglia through interaction with HSP70/TLR4, αVβ3/αVβ5, and P2X4R signalling pathways and that these effects depend on the integrity of lipid rafts. Our findings could be used for development of new therapeutic strategies targeting disease-associated microglia.

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The role of microglial autophagy in Parkinson’s disease

Cited by 13 publications

References 90 publications

High-Mobility Group Box 1 (HMGB1) Protein in Parkinson's Disease Research: A 10-Year Bibliometric Analysis

High-Mobility Group Box 1 (HMGB1) Protein in Parkinson's Disease Research: A 10-Year Bibliometric Analysis

Microglia NLRP3 Inflammasome and Neuroimmune Signaling in Substance Use Disorders

Extracellular vesicles promote autophagy in human microglia through lipid raft-dependent mechanisms

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