Functional roles of reactive astrocytes in neuroinflammation and neurodegeneration

Nature Reviews Neurology, Год журнала: 2023, Номер 19(7), С. 395 - 409

Опубликована: Июнь 12, 2023

Язык: Английский

---

Solving neurodegeneration: common mechanisms and strategies for new treatments

Molecular Neurodegeneration, Год журнала: 2022, Номер 17(1)

Опубликована: Март 21, 2022

Across neurodegenerative diseases, common mechanisms may reveal novel therapeutic targets based on neuronal protection, repair, or regeneration, independent of etiology site disease pathology. To address these and discuss emerging treatments, in April, 2021, Glaucoma Research Foundation, BrightFocus the Melza M. Frank Theodore Barr Foundation collaborated to bring together key opinion leaders experts field for a virtual meeting titled "Solving Neurodegeneration". This "think-tank" style focused uncovering mechanistic roots promising new catalyzed by goal finding treatments glaucoma, world's leading cause irreversible blindness interest three hosting foundations. Glaucoma, which causes vision loss through degeneration optic nerve, likely shares early cellular molecular events with other diseases central nervous system. Here we major areas overlap between system: neuroinflammation, bioenergetics metabolism, genetic contributions, neurovascular interactions. We summarize important discussion points emphasis research that are most innovative treatment neurodegeneration yet require further development. The is highlighted provides unique opportunities collaboration will lead efforts preventing ultimately loss.

Язык: Английский

---

Astrocytes in human central nervous system diseases: a frontier for new therapies

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Окт. 13, 2023

Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence the central nervous system (CNS). contribute pathophysiology all neurological neuropsychiatric disorders in ways that can be either beneficial or detrimental disorder outcome. Pathophysiological changes astroglia primary secondary result gain loss functions. respond external, non-cell autonomous signals associated with any form CNS pathology by undergoing complex variable their structure, molecular expression, function. In addition, internally driven, cell astroglial innate properties lead pathologies. Astroglial is complex, different pathophysiological states phenotypes context-specific vary disorder, disorder-stage, comorbidities, age, sex. Here, we classify into (i) reactive astrogliosis, (ii) atrophy function, (iii) degeneration death, (iv) astrocytopathies characterised aberrant forms drive disease. We review across spectrum human diseases disorders, including neurotrauma, stroke, neuroinfection, autoimmune attack epilepsy, as well neurodevelopmental, neurodegenerative, metabolic disorders. Characterising cellular mechanisms represents new frontier identify novel therapeutic strategies.

Язык: Английский

---

Single-cell and spatial transcriptomics: deciphering brain complexity in health and disease

Nature Reviews Neurology, Год журнала: 2023, Номер 19(6), С. 346 - 362

Опубликована: Май 17, 2023

Язык: Английский

---

Microglia as hackers of the matrix: sculpting synapses and the extracellular space

Cellular and Molecular Immunology, Год журнала: 2021, Номер 18(11), С. 2472 - 2488

Опубликована: Авг. 19, 2021

Abstract Microglia shape the synaptic environment in health and disease, but synapses do not exist a vacuum. Instead, pre- postsynaptic terminals are surrounded by extracellular matrix (ECM), which together with glia comprise four elements of contemporary tetrapartite synapse model. While research this area is still just beginning, accumulating evidence points toward novel role for microglia regulating ECM during normal brain homeostasis, such processes may, turn, become dysfunctional disease. As it relates to synapses, reported modify perisynaptic matrix, diffuse that surrounds dendritic axonal terminals, as well perineuronal nets (PNNs), specialized reticular formations compact enwrap neuronal subsets stabilize proximal synapses. The interconnected relationship between they embedded suggests alterations one structure necessarily affect dynamics other, may need sculpt within. Here, we provide an overview microglial regulation PNNs, propose candidate mechanisms these structures be modified, present implications modifications homeostasis

Язык: Английский

---

CRISPRi screens in human iPSC-derived astrocytes elucidate regulators of distinct inflammatory reactive states

Nature Neuroscience, Год журнала: 2022, Номер 25(11), С. 1528 - 1542

Опубликована: Окт. 27, 2022

Язык: Английский

---

The Neurovasculome: Key Roles in Brain Health and Cognitive Impairment: A Scientific Statement From the American Heart Association/American Stroke Association

Stroke, Год журнала: 2023, Номер 54(6)

Опубликована: Апрель 3, 2023

Preservation of brain health has emerged as a leading public priority for the aging world population. Advances in neurovascular biology have revealed an intricate relationship among cells, meninges, and hematic lymphatic vasculature (the neurovasculome) that is highly relevant to maintenance cognitive function. In this scientific statement, multidisciplinary team experts examines these advances, assesses their relevance disease, identifies knowledge gaps, provides future directions.

Язык: Английский

---

Smart Nanomedicine to Enable Crossing Blood–Brain Barrier Delivery of Checkpoint Blockade Antibody for Immunotherapy of Glioma

ACS Nano, Год журнала: 2022, Номер 16(1), С. 664 - 674

Опубликована: Янв. 3, 2022

Immune checkpoint blockade (ICB) therapy has shown tremendous promises in the treatment of various types tumors. However, ICB with antibodies appears to be less effective for glioma, partly owing existence blood–brain barrier (BBB) that impedes entrance therapeutics including most proteins central nervous system (CNS). Herein, considering widely existing nicotinic acetylcholine receptors (nAChRs) and choline transporters (ChTs) on surface BBB, a analogue 2-methacryloyloxyethyl phosphorylcholine (MPC) is employed fabricate BBB-crossing copolymer via free-radical polymerization, followed by conjugation antiprogrammed death-ligand 1 (anti-PD-L1) pH-sensitive traceless linker. The obtained nanoparticles exhibit significantly improved capability receptor-mediated transportation after intravenous injection an orthotopic glioma tumor model. Within acidic microenvironment, anti-PD-L1 would released from such pH-responsive nanoparticles, further triggering highly prolong animal survival. This work thus realizes microenvironment responsive delivery antibodies, promising next generation immunotherapy glioma.

Язык: Английский

---

The immunomodulatory mechanisms for acupuncture practice

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Апрель 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.

Язык: Английский

---

Droplet-based forward genetic screening of astrocyte–microglia cross-talk

Science, Год журнала: 2023, Номер 379(6636), С. 1023 - 1030

Опубликована: Март 10, 2023

Cell-cell interactions in the central nervous system play important roles neurologic diseases. However, little is known about specific molecular pathways involved, and methods for their systematic identification are limited. Here, we developed a forward genetic screening platform that combines CRISPR-Cas9 perturbations, cell coculture picoliter droplets, microfluidic-based fluorescence-activated droplet sorting to identify mechanisms of cell-cell communication. We used SPEAC-seq (systematic perturbation encapsulated associated cells followed by sequencing), combination with vivo microglia-produced amphiregulin as suppressor disease-promoting astrocyte responses multiple sclerosis preclinical models clinical samples. Thus, enables high-throughput communication mechanisms.

Язык: Английский

---