Neuron, Journal Year: 2023, Volume and Issue: 111(14), P. 2155 - 2169.e9
Published: May 5, 2023
Language: Английский
Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)
Published: July 12, 2023
Abstract Studies in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and Amyotrophic lateral sclerosis, Huntington’s so on, have suggested that inflammation is not only a result of neurodegeneration but also crucial player this process. Protein aggregates which are very common pathological phenomenon can induce neuroinflammation further aggravates protein aggregation neurodegeneration. Actually, even happens earlier than aggregation. Neuroinflammation induced by genetic variations CNS cells or peripheral immune may deposition some susceptible population. Numerous signaling pathways range been to be involved the pathogenesis neurodegeneration, although they still far from being completely understood. Due limited success traditional treatment methods, blocking enhancing inflammatory considered promising strategies for therapy many them got exciting results animal models clinical trials. Some them, few, approved FDA usage. Here we comprehensively review factors affecting major pathogenicity sclerosis. We summarize current strategies, both clinic, diseases.
Language: Английский
Citations
577
Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(9), P. 563 - 579
Published: March 15, 2023
Macrophages are innate immune cells that form a 3D network in all our tissues, where they phagocytose dying and cell debris, complexes, bacteria other waste products. Simultaneously, produce growth factors signalling molecules — such activities not only promote host protection response to invading microorganisms but also crucial for organ development homeostasis. There is mounting evidence of macrophages orchestrating fundamental physiological processes, as blood vessel formation, adipogenesis, metabolism central peripheral neuronal function. In parallel, novel methodologies have led the characterization tissue-specific macrophages, with distinct subpopulations these showing different developmental trajectories, transcriptional programmes life cycles. Here, we summarize growing knowledge macrophage diversity how subsets orchestrate tissue We further interrelate ontogeny their core functions across is, events within niche may control functionality during development, homeostasis ageing. Finally, highlight open questions will need be addressed by future studies better understand subsets. important immunity infections clearing products from maintain health regulating metabolism, many biological processes. Elvira Mass co-workers discuss populations found throughout body, highlighting shared unique aspects functions.
Language: Английский
Citations
313
Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)
Published: Feb. 16, 2024
Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management
Language: Английский
Citations
274
Cell, Journal Year: 2023, Volume and Issue: 186(8), P. 1689 - 1707
Published: April 1, 2023
The nervous system governs both ontogeny and oncology. Regulating organogenesis during development, maintaining homeostasis, promoting plasticity throughout life, the plays parallel roles in regulation of cancers. Foundational discoveries have elucidated direct paracrine electrochemical communication between neurons cancer cells, as well indirect interactions through neural effects on immune stromal cells tumor microenvironment a wide range malignancies. Nervous system-cancer can regulate oncogenesis, growth, invasion metastatic spread, treatment resistance, stimulation tumor-promoting inflammation, impairment anti-cancer immunity. Progress neuroscience may create an important new pillar therapy.
Language: Английский
Citations
217
Cell, Journal Year: 2023, Volume and Issue: 186(20), P. 4260 - 4270
Published: Sept. 1, 2023
Language: Английский
Citations
134
Cell, Journal Year: 2023, Volume and Issue: 186(17), P. 3706 - 3725.e29
Published: Aug. 1, 2023
The bone marrow in the skull is important for shaping immune responses brain and meninges, but its molecular makeup among bones relevance human diseases remain unclear. Here, we show that mouse has most distinct transcriptomic profile compared with other states of health injury, characterized by a late-stage neutrophil phenotype. In humans, proteome analysis reveals distinct, differentially expressed neutrophil-related pathways unique synaptic protein signature. 3D imaging demonstrates structural cellular details skull-meninges connections (SMCs) veins. Last, using translocator positron emission tomography (TSPO-PET) imaging, reflects inflammatory disease-specific spatial distribution patients various neurological disorders. anatomical functional potential as site diagnosing, monitoring, treating diseases.
Language: Английский
Citations
76
Nature, Journal Year: 2024, Volume and Issue: 626(8001), P. 1108 - 1115
Published: Feb. 7, 2024
Abstract Psychosocial stress has profound effects on the body, including immune system and brain 1,2 . Although a large number of pre-clinical clinical studies have linked peripheral alterations to stress-related disorders such as major depressive disorder (MDD) 3 , underlying mechanisms are not well understood. Here we show that expression circulating myeloid cell-specific proteinase, matrix metalloproteinase 8 (MMP8), is increased in serum humans with MDD stress-susceptible mice following chronic social defeat (CSDS). In mice, this increase leads extracellular space neurophysiological changes nucleus accumbens (NAc), altered behaviour. Using combination mass cytometry single-cell RNA sequencing, performed high-dimensional phenotyping cells circulation demonstrate monocytes strongly affected by stress. both traffic showed Mmp8 We further MMP8 directly infiltrates NAc parenchyma controls ultrastructure space. Depleting prevented stress-induced avoidance behaviour neurophysiology Collectively, these data establish mechanism which factors can affect central nervous function context Targeting specific cell-derived metalloproteinases could constitute novel therapeutic targets for neuropsychiatric disorders.
Language: Английский
Citations
67
Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(3), P. 531 - 549
Published: Feb. 26, 2024
Language: Английский
Citations
29
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: March 5, 2024
Abstract The human subarachnoid space harbors the cerebrospinal fluid, which flows within a landscape of blood vessels and trabeculae. Functional implications anatomy remain far less understood. This study 75 patients utilizes fluid tracer (gadobutrol) consecutive magnetic resonance imaging to investigate features early (i.e. 2-3 h after injection) propagation space. There is time-dependent perivascular pattern enrichment antegrade along major cerebral artery trunks; anterior-, middle-, posterior arteries. correlation between time first around arteries in nearby cortex significant. These observations suggest existence compartmentalized space, where ensheathment facilitates passage towards brain tissue. Periarterial transport impaired subjects with reduced intracranial pressure-volume reserve capacity idiopathic normal pressure hydrocephalus who also show increased size.
Language: Английский
Citations
29
Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 9, 2024
Language: Английский
Citations
28