Blood-brain barrier dysfunction and Alzheimer’s disease: associations, pathogenic mechanisms, and therapeutic potential DOI Creative Commons
Yanting Chen,

Yanfang He,

Jinling Han

и другие.

Frontiers in Aging Neuroscience, Год журнала: 2023, Номер 15

Опубликована: Ноя. 13, 2023

Alzheimer’s disease (AD) is a common neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ), hyperphosphorylation tau, and neuroinflammation in brain. The blood–brain barrier (BBB) limits solutes from circulating blood entering brain, which essential for neuronal functioning. Focusing on BBB function important early detection AD in-depth study pathogenic mechanisms. However, mechanism alteration still unclear, hinders further research therapeutics that target to delay progression AD. exact timing vascular abnormalities complex cause-and-effect relationships remain uncertain. Thus, it necessary summarize emphasize this process. First, review, current evidence dysfunction summarized. Then, interrelationships mechanisms between risk factors AD, such as Aβ, neuroinflammation, apolipoprotein E (ApoE) genotype aging, were analyzed. Finally, we discuss status future directions therapeutic strategies targeting BBB. We hope these summaries or reviews will allow readers better understand relationship

Язык: Английский

Anti-Inflammatory Effects of GLP-1 Receptor Activation in the Brain in Neurodegenerative Diseases DOI Open Access
Yolanda Diz-Chaves,

Zainab Mastoor,

Carlos Spuch

и другие.

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(17), С. 9583 - 9583

Опубликована: Авг. 24, 2022

The glucagon-like peptide-1 (GLP-1) is a pleiotropic hormone well known for its incretin effect in the glucose-dependent stimulation of insulin secretion. However, GLP-1 also produced brain and displays critical role neuroprotection inflammation by activating receptor signaling pathways. Several studies vivo vitro using preclinical models neurodegenerative diseases show that GLP-1R activation has anti-inflammatory properties. This review explores molecular mechanistic action RAS relation to brain. These findings update our knowledge potential benefits GLP-1RAS actions reducing inflammatory response. molecules emerge as therapeutic tool treating neuroinflammatory pathologies.

Язык: Английский

Процитировано

55

Clonal hematopoiesis, somatic mosaicism, and age-associated disease DOI
Megan A. Evans, Kenneth Walsh

Physiological Reviews, Год журнала: 2022, Номер 103(1), С. 649 - 716

Опубликована: Сен. 1, 2022

Somatic mosaicism, the occurrence of multiple genetically distinct cell clones within same tissue, is an evitable consequence human aging. The hematopoietic system no exception to this, where studies have revealed presence expanded blood carrying mutations in preleukemic driver genes and/or genetic alterations chromosomes. This phenomenon referred as clonal hematopoiesis and remarkably prevalent elderly individuals. While represents early step toward a hematological malignancy, most individuals will never develop cancer. Somewhat unexpectedly, epidemiological found that associated with increase risk all-cause mortality age-related disease, particularly cardiovascular system. Studies using murine models begun shed light on this relationship, suggesting mature cells can causally contribute aging disease by augmenting inflammatory processes. Here we provide up-to-date review context somatic mosaicism describe recent reported associations disease. We also discuss experimental provided important mechanistic insight into how promote knowledge could be leveraged treat hematopoiesis.

Язык: Английский

Процитировано

53

Neuroinflammation: A Possible Link Between Chronic Vascular Disorders and Neurodegenerative Diseases DOI Creative Commons
Emmanuel Moyse, Slavica Krantic,

Nesrine Djellouli

и другие.

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

Опубликована: Май 19, 2022

Various age-related diseases involve systemic inflammation, i.e. a stereotyped series of acute immune system responses, and aging itself is commonly associated with low-grade inflammation or inflamm’aging. Neuroinflammation defined as inflammation-like processes inside the central nervous system, which this review discusses possible link between cardiovascular disease-related chronic neurodegenerative diseases. To aim, neuroinflammation mechanisms are first summarized, encompassing cellular effectors molecular mediators. A comparative survey best-known physiological contexts (neurodegenerative transient ischemia) reveals some common features such microglia activation. The recently published transcriptomic characterizations have pointed marker core signature among diseases, but also unraveled discrepancies neuroinflammations related vascular origin. We next links neuroinflammation, beginning respective pro-inflammatory cells, macrophages microglia. Finally, we point out gap knowledge concerning atherosclerosis-related for most surprising given that atherosclerosis established major risk factor

Язык: Английский

Процитировано

51

Identification of immune microenvironment subtypes and signature genes for Alzheimer’s disease diagnosis and risk prediction based on explainable machine learning DOI Creative Commons

Yongxing Lai,

Peiqiang Lin,

Fan Lin

и другие.

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Дек. 8, 2022

Background Using interpretable machine learning, we sought to define the immune microenvironment subtypes and distinctive genes in AD. Methods ssGSEA, LASSO regression, WGCNA algorithms were used evaluate state AD patients. To predict fate of identify genes, six learning developed. The output models was interpreted using SHAP LIME algorithms. For external validation, four separate GEO databases used. We estimated subgroups immunological unsupervised clustering. Further research done on variations microenvironment, enhanced functions pathways, therapeutic medicines between these subtypes. Finally, expression characteristic verified AlzData pan-cancer RT-PCR analysis. Results It determined that is connected changes microenvironment. revealed 31 potential which greenyellow blue modules shown be most associated with infiltrated cells. In testing set, XGBoost algorithm had best performance an AUC 0.86 a P-R value 0.83. Following screening set by verification independent datasets, five (CXCR4, PPP3R1, HSP90AB1, CXCL10, S100A12) closely pathological biomarkers allowed for accurate prediction progression found microenvironment-related genes. feature gene-based nomogram may provide clinical advantages Two patients identified, subtype2 linked metabolic phenotype, subtype1 belonged immune-active kind. MK-866 arachidonyltrifluoromethane identified as top treatment agents 1 2, respectively. These distinguishing intimately development disease, according Alzdata database, research, Conclusion hub are strongly pathology CXCR4, S100A12. hypothesized molecular might offer novel perceptions individualized treatment.

Язык: Английский

Процитировано

47

Blood-brain barrier dysfunction and Alzheimer’s disease: associations, pathogenic mechanisms, and therapeutic potential DOI Creative Commons
Yanting Chen,

Yanfang He,

Jinling Han

и другие.

Frontiers in Aging Neuroscience, Год журнала: 2023, Номер 15

Опубликована: Ноя. 13, 2023

Alzheimer’s disease (AD) is a common neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ), hyperphosphorylation tau, and neuroinflammation in brain. The blood–brain barrier (BBB) limits solutes from circulating blood entering brain, which essential for neuronal functioning. Focusing on BBB function important early detection AD in-depth study pathogenic mechanisms. However, mechanism alteration still unclear, hinders further research therapeutics that target to delay progression AD. exact timing vascular abnormalities complex cause-and-effect relationships remain uncertain. Thus, it necessary summarize emphasize this process. First, review, current evidence dysfunction summarized. Then, interrelationships mechanisms between risk factors AD, such as Aβ, neuroinflammation, apolipoprotein E (ApoE) genotype aging, were analyzed. Finally, we discuss status future directions therapeutic strategies targeting BBB. We hope these summaries or reviews will allow readers better understand relationship

Язык: Английский

Процитировано

36