Neurochemistry International, Год журнала: 2024, Номер unknown, С. 105917 - 105917
Опубликована: Дек. 1, 2024
Язык: Английский
Frontiers in Cellular Neuroscience, Год журнала: 2024, Номер 18
Опубликована: Фев. 28, 2024
Traumatic brain injury (TBI) is one of the most common pathological conditions impacting central nervous system (CNS). A neurological deficit associated with TBI results from a complex pathogenetic mechanisms including glutamate excitotoxicity, inflammation, demyelination, programmed cell death, or development edema. The critical components contributing to CNS response, damage control, and regeneration after are glial cells–in reaction tissue damage, their activation, hypertrophy, proliferation occur, followed by formation scar. scar creates barrier in damaged helps protect acute phase post-injury. However, this process prevents complete recovery late/chronic producing permanent scarring, which significantly impacts function. Various types participate formation, but mostly attributed reactive astrocytes microglia, play important roles several pathologies. Novel technologies whole-genome transcriptomic epigenomic analyses, unbiased proteomics, show that both microglia represent groups heterogenic subpopulations different genomic functional characteristics, responsible for role neurodegeneration, neuroprotection regeneration. Depending on representation distinct glia subpopulations, as well regenerative processes delayed neurodegeneration may thus differ nearby remote areas structures. This review summarizes process, where resultant effect severity-, region- time-dependent determined model distance explored area lesion site. Here, we also discuss findings concerning intercellular signaling, long-term possibilities novel therapeutical approaches. We believe comprehensive study an emphasis cells, involved post-injury processes, be helpful further research decisive factor when choosing model.
Язык: Английский
Процитировано
19
Glia, Год журнала: 2022, Номер 71(3), С. 571 - 587
Опубликована: Ноя. 10, 2022
Inflammation is a common feature in neurodegenerative diseases that contributes to neuronal loss. Previously, we demonstrated the basal inflammatory tone differed between brain regions and, consequently, reaction generated pro-inflammatory stimulus was different. In this study, assessed innate immune midbrain and striatum using an experimental model of Parkinson's disease. An adeno-associated virus serotype 9 expressing α-synuclein mCherry genes or gene administered into substantia nigra. Myeloid cells (CD11b+ ) astrocytes (ACSA2+ were purified from for bulk RNA sequencing. parkinsonian midbrain, CD11b+ presented unique anti-inflammatory transcriptomic profile degenerative microglia signatures described models other conditions. By contrast, striatal showed state similar disease-associated microglia. prominent increase infiltrated monocytes/macrophages observed together with microglia, participated actively phagocytosis dopaminergic bodies. Although phagocytic profile, morphology cell density preserved no active detected. Interestingly, fingerprint low number differentially displayed transcripts striatum. During α-synuclein-dependent degeneration, experience context-dependent activation states different contribution reaction. Our results point towards relevance selecting appropriate targets design neuroprotective strategies aimed modulate system during phase degeneration.
Язык: Английский
Процитировано
43
Trends in Neurosciences, Год журнала: 2023, Номер 46(10), С. 863 - 878
Опубликована: Авг. 17, 2023
Язык: Английский
Процитировано
33
Frontiers in Network Physiology, Год журнала: 2023, Номер 3
Опубликована: Июнь 1, 2023
Neuronal signalling is a key element in neuronal communication and essential for the proper functioning of CNS. Astrocytes, most prominent glia brain play role modulating at molecular, synaptic, cellular, network levels. Over past few decades, our knowledge about astrocytes their has evolved from considering them as merely glue that provides structural support to neurons, elements. Astrocytes can regulate activity neurons by controlling concentrations ions neurotransmitters extracellular milieu, well releasing chemicals gliotransmitters modulate activity. The aim this review summarise main processes through which are function. We will systematically distinguish between direct indirect pathways affect all Lastly, we summarize pathological conditions arise once these impaired focusing on neurodegeneration.
Язык: Английский
Процитировано
32
Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)
Опубликована: Янв. 12, 2024
The intracellular deposition and intercellular transmission of α-synuclein (α-syn) are shared pathological characteristics among neurodegenerative disorders collectively known as α-synucleinopathies, including Parkinson's disease (PD). Although the precise triggers α-synucleinopathies remain unclear, recent findings indicate that disruption microglial homeostasis contributes to pathogenesis PD. Microglia play a crucial role in maintaining optimal neuronal function by ensuring homeostatic environment, but this is disrupted during progression α-syn pathology. involvement microglia accumulation, uptake, clearance aggregated proteins critical for managing spread caused This review summarizes current knowledge on interrelationships between focusing remarkable ability recognize internalize extracellular through diverse pathways. process intracellularly intercellularly facilitate aggregation cell-to-cell propagation. conformational state distinctly influences inflammation, which can affect peripheral immune cells such macrophages lymphocytes may regulate α-synucleinopathies. We also discuss ongoing research efforts identify potential therapeutic approaches targeting both accumulation inflammation Video Abstract.
Язык: Английский
Процитировано
7
npj Parkinson s Disease, Год журнала: 2025, Номер 11(1)
Опубликована: Апрель 11, 2025
Iron deposition in the nigrostriatal system plays a pivotal role Parkinson's disease (PD) onset and progression. This study explored time course of iron accumulation 54 PD patients at early to moderately advanced stages 20 age-matched healthy controls. Using multi-echo T2*-MRI R2* relaxometry, content was assessed substantia nigra pars compacta (SNpc) striatum. In vivo findings were contrasted with histological analyses progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism model involving six non-human primates (NHPs) two controls using Perls' Prussian blue staining. Complementarily, dopaminergic degeneration quantified by 6-[18F]-fluoro-L-dopa PET humans TH immunohistochemistry NHPs. Results showed SNpc correlating striatal denervation neuronal loss. Striatal followed V-shaped progression, decreasing initially increasing later. may serve as marker neurodegeneration PD, while decreased indicate pathological susceptibility
Язык: Английский
Процитировано
1
CNS Neuroscience & Therapeutics, Год журнала: 2023, Номер 30(3)
Опубликована: Окт. 30, 2023
Abstract Background Gemfibrozil (Gem) is a drug that has been shown to activate PPAR‐α, nuclear receptor plays key role in regulating lipid metabolism. Gem used lower the levels of triglycerides and reduce risk coronary heart disease patients. Experimental studies vitro vivo have can prevent or slow progression neurological disorders (NDs), including cerebral ischemia (CI), Alzheimer's (AD), Parkinson's (PD), multiple sclerosis (MS). Neuroinflammation known play significant these disorders. Method The literature review for this study was conducted by searching Scopus, Science Direct, PubMed, Google Scholar databases. Result results show neuroprotective effects through several cellular molecular mechanisms such as: (1) ability upregulate pro‐survival factors (PGC‐1α TFAM), promoting survival function mitochondria brain, (2) strongly inhibits activation NF‐κB, AP‐1, C/EBPβ cytokine‐stimulated astroglial cells, which are increase expression iNOS production NO response proinflammatory cytokines, (3) protects dopamine neurons MPTP mouse model PD increasing PPARα, turn stimulates GDNF astrocytes, (4) reduces amyloid plaque pathology, activity glial improves memory, (5) increases myelin genes (MBP CNPase) via PPAR‐β, (6) hippocampal BDNF counteract depression. Conclusion According study, investigated its potential therapeutic effect NDs. Further research needed fully understand
Язык: Английский
Процитировано
17
Frontiers in Neuroscience, Год журнала: 2023, Номер 17
Опубликована: Дек. 22, 2023
Microglia are immune cells within the central nervous system (CNS) closely linked to brain health and neurodegenerative diseases such as Alzheimer’s disease Parkinson’s disease. In response changes in surrounding environment, microglia activate change their state function. Several factors, example for circadian rhythm disruption development of diseases, influence activation. this review, we explore microglia’s function associated neural mechanisms. We elucidate that rhythms essential factors influencing activation Circadian affects and, consequently, diseases. addition, found abnormal is a common feature an factor development. Here highlight importance Targeting treatment promising direction. introduce progress methods targeting summarize drugs developed with targets, hoping provide new ideas treating
Язык: Английский
Процитировано
17
Life Sciences, Год журнала: 2023, Номер 328, С. 121920 - 121920
Опубликована: Июль 8, 2023
Язык: Английский
Процитировано
15
Scientific Reports, Год журнала: 2023, Номер 13(1)
Опубликована: Дек. 13, 2023
LRRK2-G2019S is one of the most common Parkinson's disease (PD)-associated mutations and has been shown to alter microglial functionality. However, impact on transcriptional profile human induced pluripotent stem cell-derived microglia-like cells (iMGLs) how it corresponds microglia in idiopathic PD brain not known. Here we demonstrate that carrying iMGL recapitulate aspects signature midbrain microglia. subtle donor-dependent alterations mitochondrial respiration, phagocytosis cytokine secretion. Investigation state midbrains patients revealed a subset with overlap between vitro PD-iMGL We conclude serve as model study PD-related effects
Язык: Английский
Процитировано
12