The Latest Articles on Neuroinflammation and Neurodegenerative Diseases

Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.

This week, we would like to share several latest articles on Neuroinflammation and Neurodegenerative Diseases.

Title: The role of dopamine in NLRP3 inflammasome inhibition: implications for neurodegenerative diseases

Authors: Possemato Elena, La Barbera Livia, Nobili Annalisa, Krashia Paraskevi, Krashia Paraskevi

Type: Review

Abstract:

In the Central Nervous System (CNS), neuroinflammation orchestrated by microglia and astrocytes is an innate immune response to counteract stressful and dangerous insults. One of the most important and best characterized players in the neuroinflammatory response is the NLRP3 inflammasome, a multiproteic complex composed by NOD-like receptor family Pyrin domain containing 3 (NLRP3), apoptosis-associated speck–like protein (ASC) and pro-caspase-1. Different stimuli mediate NLRP3 activation, resulting in the NLRP3 inflammasome assembly and the pro-inflammatory cytokine (IL-1β and IL-18) maturation and secretion. The persistent and uncontrolled NLRP3 inflammasome activation has a leading role during the pathophysiology of neuroinflammation in age-related neurodegenerative diseases such as Parkinson's (PD) and Alzheimer's (AD).

The neurotransmitter dopamine (DA) is one of the players that negatively modulate NLRP3 inflammasome activation through DA receptors expressed in both microglia and astrocytes.

This review summarizes recent findings linking the role of DA in the modulation of NLRP3-mediated neuroinflammation in PD and AD, where early deficits of the dopaminergic system are well characterized.

Highlighting the relationship between DA, its glial receptors and the NLRP3-mediated neuroinflammation can provide insights to novel diagnostic strategies in early disease phases and new pharmacological tools to delay the progression of these diseases.

Access this article: https://doi.org/10.1016/j.arr.2023.101907

Title: Amyloid-β/Tau burden and neuroinflammation dual-targeted nanomedicines synergistically restore memory and recognition of Alzheimer's disease mice

Authors: Lingxiao Zhang, Lingxiao Zhang, Fatemeh Movahedi, Zijin Li, Li Li, Jing Hu, Yingbo Jia, Yaru Huang, Yaru Huang, Jie Zhu, Xiaoying Sun, Linghui Zeng, Ruitian Liu, Zhi Ping Xu

Type: Research Article

Abstract:

Efficient multi-targeted intervention of complex pathogenic factors may hold promises for Alzheimer's disease (AD) treatment due to the continuous failure of single-targeted therapy in clinics. To this end, we developed two dual-targeted layered double hydroxide (LDH) nanoparticle (NP)-based nanomedicines in this research for simultaneously reducing amyloid β (Aβ)/hyperphosphorylated Tau burden and neuroinflammation. LDH NPs were first loaded with two therapeutics, i.e. Rutin and β-site amyloid precursor protein cleaving enzyme-1 (BACE1) or glycogen synthase kinase 3β (GSK3β) siRNA. The nanomedicines were further functionalized with Ang2 and RVG29 via adsorption of their bovine serum albumin (BSA) conjugates. In APP/PS1 and Tau.P301S AD mouse models, nanomedicines efficiently silenced the target genes and decreased the expression of abnormal Aβ and hyperphosphorylated Tau, respectively. Moreover, the co-delivered Rutin inhibited the Aβ aggregation and normalized the functions of microglia and astrocytes to reduce neuroinflammation, synergistically recovering the memory and cognitive deficits of AD mice, comparable to that of wide type mice. The successful AD treatment using the dual-targeted LDH nanomedicines provides a paradigm for the development of multi-targeted nanomedicines and warrants further study to combat AD with the complex pathogenic mechanisms.

Access this article: https://doi.org/10.1016/j.nantod.2023.101788

Title: Sea buckthorn polysaccharide ameliorates high-fat diet induced mice neuroinflammation and synaptic dysfunction via regulating gut dysbiosis

Authors: Ying Lan, Zhiyuan Ma, Lili Chang, Jing Peng, Mengqi Zhang, Qingyang Sun, Ruixue Qiao, Xinglin Hou, Xuechao Ding, Qiang Zhang, Qiang Peng, Juane Dong, Xuebo Liu

Type: Review

Abstract:  

Currently, definitive treatment for neurodegenerative diseases without side effects has not been developed, therefore, exploring natural polysaccharides with neuroprotection to prevent the occurrences and progressions of cognitive dysfunctions has important significance. The purpose of this study was to investigate the effects of sea buckthorn polysaccharide (SBP) on high-fat diet (HFD) induced mice cognitive dysfunctions and attempted to explore its biological mechanisms. Behavior tests (Y-maze and Barnes maze) suggested that SBP effectively alleviated the HFD induced behavioral disorders, which was in accordance with the inhibition of neuroinflammation via suppressing the NF-κB pathway and amelioration of synaptic dysfunction via upregulating CREB/BDNF/TrkB pathway in mice brain. Furthermore, SBP alleviated the gut barrier impairment, inflammatory responses, and lipopolysaccharide invasion into blood circulation via regulating the gut microbiome structure, especially correcting the reduction of Ileibacterium and increase of Lactobacillus, Dubosiella, Olsenella, Helicobacter, and Ruminiclostridium_9 in HFD mice. Therefore, the reversal effects of SBP on gut dysbiosis might be the important reason for its positive effects on cognitive dysfunction induced by HFD in mice.

Access this article: https://doi.org/10.1016/j.ijbiomac.2023.123797

Title: Low-dose ketamine inhibits neuronal apoptosis and neuroinflammation in PC12 cells via α7nAChR mediated TLR4/MAPK/NF-κB signaling pathway

Authors: Jinghua Zhao, Ruxin Zhang, Ruxin Zhang, Sheng Jiang, Huimei Liang, Chen Guo, Chen Guo, Huan Zeng, Houhui Song

Type: Research Article

Abstract:

Ketamine is commonly used for sedation, analgesia and anesthetics. Much evidence has shown that it has an immune-regulatory effect. The cholinergic anti-inflammatory pathway mediated by α7nAChR is a prominent target of anti-inflammatory therapy. However, whether ketamine suppresses inflammatory levels in nerve cells by activating α7nAChR remains unknown. Lipopolysaccharide (LPS) was used to establish the neuroinflammation model in PC12 cells in vitro, and α7nAChR siRNA was transfected into PC12 cells 30 min before LPS to inhibit gene expression of α7nAChR. PC12 cells were stimulated with LPS for 24 h, and the indicators were detected at 2 h after GTS-21 and ketamine were added. The results showed that LPS increased the proportion of PC12 cells apoptosis, activated TLR4/MAPK/NF-κB signaling pathway, and increased the expression of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Ketamine reduced the ratio of early apoptosis and late apoptosis of PC12, inhibited the entry of P65 into the nucleus, decreased the activation of TLR4/MAPK/NF-κB and improved neuroinflammation. However, the ameliorating effects of ketamine on neuronal apoptosis and neuroinflammation were inhibited in the α7nAChRi group. This indicated that α7nAChR played a key role in the anti-inflammatory process of ketamine. Low-dose ketamine inhibited TLR4/MAPK/NF-κB by activating the α7nAChR-mediated cholinergic anti-inflammatory pathway, thereby producing the protective effect on neuronal apoptosis and neuroinflammation.

Access this article: https://doi.org/10.1016/j.intimp.2023.109880 

Title: Pesticides at brain borders: Impact on the blood-brain barrier, neuroinflammation, and neurological risk trajectories

Authors: Noemie Cresto, Isabel Forner-Piquer, Asma Baig, Mousumi Chatterjee, Julie Perroy, Jacopo Goracci, Nicola Marchi

Type: Review

Abstract:

Pesticides are omnipresent, and they pose significant environmental and health risks. Translational studies indicate that acute exposure to high pesticide levels is detrimental, and prolonged interaction with low-level pesticides, as single and cocktail, could represent a risk factor for multi-organ pathophysiology, including the brain. Within this research template, we focus on pesticides' impact on the blood-brain barrier (BBB) and neuroinflammation, physical and immunological borders for the homeostatic control of the central nervous system (CNS) neuronal networks. We examine the evidence supporting a link between pre- and postnatal pesticide exposure, neuroinflammatory responses, and time-depend vulnerability footprints in the brain. Because of the pathological role of BBB damage and inflammation on neuronal transmission from early development, varying exposures to pesticides could represent a danger, perhaps accelerating adverse neurological trajectories during aging. Refining our understanding of how pesticides influence brain barriers and borders could enable the implementation of pesticide-specific regulatory measures directly relevant to environmental neuroethics, the exposome, and one-health frameworks.

Access this article: https://doi.org/10.1016/j.chemosphere.2023.138251