Role of neuroinflammation in neurodegeneration development

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

Опубликована: Июль 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.

Язык: Английский

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Biological aging processes underlying cognitive decline and neurodegenerative disease

Journal of Clinical Investigation, Год журнала: 2022, Номер 132(10)

Опубликована: Май 15, 2022

Alzheimer's disease and related dementias (ADRD) are among the top contributors to disability mortality in later life. As with many chronic conditions, aging is single most influential factor development of ADRD. Even older adults who remain free dementia throughout their lives, cognitive decline neurodegenerative changes appreciable advancing age, suggesting shared pathophysiological mechanisms. In this Review, we provide an overview cognition, brain morphology, neuropathological protein accumulation across lifespan humans, complementary mechanistic evidence from animal models. Next, highlight selected processes that differentially regulated disease, including aberrant autophagy, mitochondrial dysfunction, cellular senescence, epigenetic changes, cerebrovascular inflammation, lipid dysregulation. We summarize research clinical translational studies link biological underlying ADRD pathogenesis. Targeting fundamental may represent a yet relatively unexplored avenue attenuate both age-related Collaboration fields geroscience neuroscience, coupled new models more closely align human processes, necessary advance novel therapeutic discovery realm.

Язык: Английский

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Astrocyte Endfeet in Brain Function and Pathology: Open Questions

Annual Review of Neuroscience, Год журнала: 2023, Номер 46(1), С. 101 - 121

Опубликована: Фев. 28, 2023

Astrocyte endfeet enwrap the entire vascular tree within central nervous system, where they perform important functions in regulating blood-brain barrier (BBB), cerebral blood flow, nutrient uptake, and waste clearance. Accordingly, astrocyte contain specialized organelles proteins, including local protein translation machinery highly organized scaffold which anchor channels, transporters, receptors, enzymes critical for astrocyte-vascular interactions. Many neurological diseases are characterized by loss of polarization specific endfoot dysregulation, BBB disruption, altered clearance, or, extreme cases, coverage. A role has been demonstrated or postulated many these conditions. This review provides an overview development, composition, function, pathological changes highlights gaps our knowledge that future research should address.

Язык: Английский

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Cerebrospinal fluid proteomics in patients with Alzheimer’s disease reveals five molecular subtypes with distinct genetic risk profiles

Nature Aging, Год журнала: 2024, Номер 4(1), С. 33 - 47

Опубликована: Янв. 9, 2024

Abstract Alzheimer’s disease (AD) is heterogenous at the molecular level. Understanding this heterogeneity critical for AD drug development. Here we define subtypes using mass spectrometry proteomics in cerebrospinal fluid, based on 1,058 proteins, with different levels individuals ( n = 419) compared to controls 187). These had alterations protein that were associated distinct processes: subtype 1 was characterized by proteins related neuronal hyperplasticity; 2 innate immune activation; 3 RNA dysregulation; 4 choroid plexus dysfunction; and 5 blood–brain barrier impairment. Each specific genetic risk variants, example, enriched TREM2 R47H. Subtypes also differed clinical outcomes, survival times anatomical patterns of brain atrophy. results indicate highlight need personalized medicine.

Язык: Английский

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Molecular biomarkers for vascular cognitive impairment and dementia

Nature Reviews Neurology, Год журнала: 2023, Номер 19(12), С. 737 - 753

Опубликована: Ноя. 13, 2023

Язык: Английский

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A single nuclear transcriptomic characterisation of mechanisms responsible for impaired angiogenesis and blood-brain barrier function in Alzheimer’s disease

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 12, 2024

Brain perfusion and blood-brain barrier (BBB) integrity are reduced early in Alzheimer's disease (AD). We performed single nucleus RNA sequencing of vascular cells isolated from AD non-diseased control brains to characterise pathological transcriptional signatures responsible for this. show that endothelial (EC) enriched expression genes associated with susceptibility AD. Increased β-amyloid is BBB impairment a dysfunctional angiogenic response related failure increased pro-angiogenic HIF1A VEGFA signalling EC. This inflammatory activation, EC senescence apoptosis. Our genomic dissection cell risk gene enrichment provides evidence role pathology suggests reducing activation restoring effective angiogenesis could reduce dysfunction contributing the genesis or progression

Язык: Английский

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The contribution of β-amyloid, Tau and α-synuclein to blood–brain barrier damage in neurodegenerative disorders

Acta Neuropathologica, Год журнала: 2024, Номер 147(1)

Опубликована: Фев. 12, 2024

Abstract Central nervous system (CNS) accumulation of fibrillary deposits made Amyloid β (A ), hyperphosphorylated Tau or α -synuclein ( -syn), present either alone in the form mixed pathology, characterizes most common neurodegenerative diseases (NDDs) as well aging brain. Compelling evidence supports that acute neurological disorders, such traumatic brain injury (TBI) and stroke, are also accompanied by increased deposition toxic A , -syn species. While contribution these pathological proteins to neurodegeneration has been experimentally ascertained, cellular molecular mechanisms driving -syn-related damage remain be fully clarified. In last few years, studies have shown may contribute inducing and/or promoting blood–brain barrier (BBB) disruption. These can affect BBB integrity directly affecting key components pericytes endothelial cells (ECs) indirectly, macrophages activation dysfunction. Here, we summarize critically discuss findings showing how NDDs, TBI stroke. We highlight need for a deeper characterization role dysfunction macrophages, ECs improve diagnosis treatment chronic disorders.

Язык: Английский

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The role of endothelial cell–pericyte interactions in vascularization and diseases

Journal of Advanced Research, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Endothelial cells (ECs) and pericytes (PCs) are crucial components of the vascular system, with ECs lining inner layer blood vessels PCs surrounding capillaries to regulate flow angiogenesis. Intercellular communication between is vital for formation, stability, function vessels. Various signaling pathways, such as endothelial growth factor/vascular factor receptor pathway platelet-derived factor-B/platelet-derived receptor-β pathway, play roles in PCs. Dysfunctional these associated various diseases, including central nervous system disorders, certain types cancers. review: This review aimed explore diverse formation reshaping focused on essential pathways that facilitate investigated how disruptions may contribute disease. Additionally, explored potential therapeutic targets, future research directions, innovative approaches, investigating impact EC-PCs novel systemic addressing resistance antiangiogenic drugs, developing medications enhance efficacy. Key scientific concepts Disordered EC-PC intercellular plays a role abnormal vessel thus contributing progression diseases development drugs. Therefore, studies interactions have high clinical relevance.

Язык: Английский

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The Emerging Role of Central and Peripheral Immune Systems in Neurodegenerative Diseases

Frontiers in Aging Neuroscience, Год журнала: 2022, Номер 14

Опубликована: Апрель 25, 2022

For decades, it has been widely believed that the blood–brain barrier (BBB) provides an immune privileged environment in central nervous system (CNS) by blocking peripheral cells and humoral factors. This view revised recent years, with increasing evidence revealing plays a critical role regulating CNS homeostasis disease. Neurodegenerative diseases are characterized progressive dysfunction loss of neurons CNS. An number studies have focused on connection between neurodegenerative diseases. On one hand, peripherally released cytokines can cross BBB, cause direct neurotoxicity contribute to activation microglia astrocytes. other also infiltrate brain participate progression neuroinflammatory high morbidity disability rate, yet there no effective therapies stop or reverse their progression. In neuroinflammation received much attention as therapeutic target for many this review, we highlight emerging systems diseases, well interactions. A better understanding may improve strategies

Язык: Английский

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Pericyte Loss in Diseases

Cells, Год журнала: 2023, Номер 12(15), С. 1931 - 1931

Опубликована: Июль 26, 2023

Pericytes are specialized cells located in close proximity to endothelial within the microvasculature. They play a crucial role regulating blood flow, stabilizing vessel walls, and maintaining integrity of blood–brain barrier. The loss pericytes has been associated with development progression various diseases, such as diabetes, Alzheimer’s disease, sepsis, stroke, traumatic brain injury. This review examines detection pericyte different explores methods employed assess coverage, elucidates potential mechanisms contributing these pathological conditions. Additionally, current therapeutic strategies targeting discussed, along future interventions aimed at preserving function promoting disease mitigation.

Язык: Английский

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