Reactive Astrocytes and Emerging Roles in Central Nervous System (CNS) Disorders DOI
Shane A. Liddelow, Michelle L. Olsen, Michael V. Sofroniew

et al.

Cold Spring Harbor Perspectives in Biology, Journal Year: 2024, Volume and Issue: 16(7), P. a041356 - a041356

Published: Feb. 5, 2024

In addition to their many functions in the healthy central nervous system (CNS), astrocytes respond CNS damage and disease through a process called "reactivity." Recent evidence reveals that astrocyte reactivity is heterogeneous spectrum of potential changes occur context-specific manner. These are determined by diverse signaling events vary not only with nature severity different insults but also location CNS, genetic predispositions, age, potentially "molecular memory" previous events. Astrocyte can be associated both essential beneficial as well harmful effects. The available information rapidly expanding much has been learned about molecular diversity reactivity. Emerging functional associations point toward roles for determining outcome disorders.

Language: Английский

The immunomodulatory mechanisms for acupuncture practice DOI Creative Commons
Meng Wang, Weili Liu,

Jiayi Ge

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: April 6, 2023

The system physiology approaches that emerge in western countries recent years echo the holistic view of ancient Traditional Chinese Medicine (TCM) practices deal with root, rather than only symptoms diseases. Particularly, TCM practices, including acupuncture, emphasize mobilization self-healing mechanisms to bring back body homeostasis. Acupuncture has been practiced for over two thousand modulate via stimulation at specific regions (acupoints). With development various research on acupuncture therapy, its regulatory effect immune gradually recognized, especially immunological diseases, infectious and allergic In this study, we reviewed immunomodulatory mechanism systematically integrates existing respectively elucidate modulatory innate system, adaptive well-known neuroanatomical mechanisms, intact somatosensory-autonomic reflex pathway. advances made systems studies, now have a great opportunity gain insight into how modulates immunity, subsequently improves efficacy.

Language: Английский

Citations

71
Molecular and metabolic heterogeneity of astrocytes and microglia DOI Creative Commons
Philip Hasel, William H. Aisenberg, F. Chris Bennett

et al.

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(4), P. 555 - 570

Published: March 22, 2023

Language: Английский

Citations

60
Adaptive design of mRNA-loaded extracellular vesicles for targeted immunotherapy of cancer DOI Creative Commons
Shiyan Dong, Xuan Liu, Ye Bi

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 19, 2023

Abstract The recent success of mRNA therapeutics against pathogenic infections has increased interest in their use for other human diseases including cancer. However, the precise delivery genetic cargo to cells and tissues remains challenging. Here, we show an adaptive strategy that enables docking different targeting ligands onto surface mRNA-loaded small extracellular vesicles (sEVs). This is achieved by using a microfluidic electroporation approach which combination nano- milli-second pulses produces large amounts IFN-γ sEVs with CD64 overexpressed on surface. molecule serves as adaptor dock ligands, such anti-CD71 anti-programmed cell death-ligand 1 (PD-L1) antibodies. resulting immunogenic (imsEV) preferentially target glioblastoma generate potent antitumour activities vivo, tumours intrinsically resistant immunotherapy. Together, these results provide engineering functionality pave way adoption cancer immunotherapy applications.

Language: Английский

Citations

51
Neuroinflammation in Alzheimer disease DOI
Wiesje M. van der Flier, Wiesje M. van der Flier,

Frank Jessen

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 9, 2024

Language: Английский

Citations

28
Contributions of Genetic Variation in Astrocytes to Cell and Molecular Mechanisms of Risk and Resilience to Late‐Onset Alzheimer's Disease DOI Creative Commons
Hyo Lee, Richard V. Pearse,

Alexandra M. Lish

et al.

Glia, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

ABSTRACT Reactive astrocytes are associated with Alzheimer's disease (AD), and several AD genetic risk variants genes highly expressed in astrocytes. However, the contribution of within to cellular processes relevant pathogenesis remains ill‐defined. Here, we present a resource for studying using large collection induced pluripotent stem cell (iPSC) lines from deeply phenotyped individuals range neuropathological cognitive outcomes. IPSC 44 were differentiated into followed by unbiased molecular profiling RNA sequencing tandem mass tag‐mass spectrometry. We demonstrate utility this examining gene‐ pathway‐level associations clinical traits, as well analyzing resilience factors through parallel analyses iPSC‐astrocytes brain tissue same individuals. Our reveal that pathways altered iPSC‐derived concordantly dysregulated tissue. This includes increased levels prefoldin proteins, extracellular matrix factors, COPI‐mediated trafficking components reduced proteins involved respiration fatty acid oxidation. Additionally, resilient high neuropathology show elevated basal interferon response secretion gamma. Correspondingly, higher polygenic scores lower study establishes an experimental system integrates information matched iPSC data cohort identify contributions affecting resilience.

Language: Английский

Citations

3
Immune modulation to treat Alzheimer’s disease DOI Creative Commons
Michael R. Duggan, David Morgan, Brittani R. Price

et al.

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 31, 2025

Abstract Immune mechanisms play a fundamental role in Alzheimer’s disease (AD) pathogenesis, suggesting that approaches which target immune cells and immunologically relevant molecules can offer therapeutic opportunities beyond the recently approved amyloid beta monoclonal therapies. In this review, we provide an overview of immunomodulatory therapeutics development, including their preclinical evidence clinical trial results. Along with detailing processes involved AD pathogenesis highlighting how these be therapeutically targeted to modify progression, summarize knowledge gained from previous trials immune-based interventions, series recommendations for development future treat AD.

Language: Английский

Citations

2
The role of endoplasmic reticulum stress in astrocytes DOI Creative Commons
Savannah G. Sims, Rylee N. Cisney,

Marissa M. Lipscomb

et al.

Glia, Journal Year: 2021, Volume and Issue: 70(1), P. 5 - 19

Published: Aug. 31, 2021

Abstract Astrocytes are glial cells that support neurological function in the central nervous system (CNS), part, by providing structural for neuronal synapses and blood vessels, participating electrical chemical transmission, trophic via soluble factors. Dysregulation of astrocyte contributes to decline CNS diseases. Neurological diseases highly heterogeneous but share common features cellular stress including accumulation misfolded proteins. Endoplasmic reticulum (ER) has been reported nearly all neurodegenerative ER occurs when there is an proteins lumen protein folding demand overwhelmed. initiates unfolded response (UPR) restore homeostasis abating translation and, if cell irreparably damaged, initiating apoptosis. Although aggregation misfolding disease well described, cell‐specific contributions UPR physiological states poorly understood. Recent work revealed a role active signaling may drive astrocytes toward maladaptive phenotype various model systems. In stress, produce inflammatory mediators, have reduced support, can transmit other cells. This review will discuss current known consequences activated astrocytes.

Language: Английский

Citations

68
Melanoma-Secreted Amyloid Beta Suppresses Neuroinflammation and Promotes Brain Metastasis DOI Open Access

Kevin Kleffman,

Grace Levinson,

Indigo V.L. Rose

et al.

Cancer Discovery, Journal Year: 2022, Volume and Issue: 12(5), P. 1314 - 1335

Published: March 9, 2022

Abstract Brain metastasis is a significant cause of morbidity and mortality in multiple cancer types represents an unmet clinical need. The mechanisms that mediate metastatic growth the brain parenchyma are largely unknown. Melanoma, which has highest rate among common types, ideal model to study how cells adapt parenchyma. Our unbiased proteomics analysis melanoma short-term cultures revealed proteins implicated neurodegenerative pathologies differentially expressed explanted from metastases compared with those derived extracranial metastases. We showed require amyloid beta (Aβ) for survival Melanoma-secreted Aβ activates surrounding astrocytes prometastatic, anti-inflammatory phenotype prevents phagocytosis by microglia. Finally, we demonstrate pharmacologic inhibition decreases burden. Significance: results reveal novel mechanistic connection between Alzheimer's disease, two previously unrelated pathologies; establish as promising therapeutic target metastasis; suppression neuroinflammation critical feature adaptation This article highlighted In Issue feature, p. 1171

Language: Английский

Citations

67
Endoplasmic Reticulum Stress-Associated Neuronal Death and Innate Immune Response in Neurological Diseases DOI Creative Commons
Mingming Shi, Yan Chai, Jianning Zhang

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 10, 2022

Neuronal death and inflammatory response are two common pathological hallmarks of acute central nervous system injury chronic degenerative disorders, both which closely related to cognitive motor dysfunction associated with various neurological diseases. Neurological diseases highly heterogeneous; however, they share a pathogenesis, that is, the aberrant accumulation misfolded/unfolded proteins within endoplasmic reticulum (ER). Fortunately, cell has intrinsic quality control mechanisms maintain proteostasis network, such as chaperone-mediated folding ER-associated degradation. However, when these fail, accumulate in ER lumen contribute stress. stress been implicated nearly all initiates unfolded protein restore proteostasis, if damage is irreversible, it elicits intracellular cascades inflammation. With growing appreciation functional association between improved understanding multiple underlying molecular mechanisms, pharmacological genetic targeting beginning emerge therapeutic approaches for

Language: Английский

Citations

52
The Gut Microbiome as a Regulator of the Neuroimmune Landscape DOI Open Access

Lewis W. Yu,

Gulistan Agirman, Elaine Y. Hsiao

et al.

Annual Review of Immunology, Journal Year: 2022, Volume and Issue: 40(1), P. 143 - 167

Published: Jan. 6, 2022

The gut microbiome influences many host physiologies, spanning gastrointestinal function, metabolism, immune homeostasis, neuroactivity, and behavior. Many microbial effects on the are orchestrated by bidirectional interactions between system. Imbalances in this dialogue can lead to dysfunction immune-mediated conditions distal organs including brain. Dysbiosis of dysregulated neuroimmune responses common comorbidities neurodevelopmental, neuropsychiatric, neurological disorders, highlighting importance microbiome-neuroimmune axis as a regulator central nervous system homeostasis. In review, we discuss recent evidence supporting role for regulating landscape health disease.

Language: Английский

Citations

50