Elevated Galectin-3 Is Associated with Aging, Multiple Sclerosis, and Oxidized Phosphatidylcholine-Induced Neurodegeneration DOI Creative Commons

Sara Xue,

Brian Lozinski, Samira Ghorbani

и другие.

Journal of Neuroscience, Год журнала: 2023, Номер 43(25), С. 4725 - 4737

Опубликована: Май 19, 2023

Aging is a significant risk factor associated with the progression of CNS neurodegenerative diseases including multiple sclerosis (MS). Microglia, resident macrophages parenchyma, are major population immune cells that accumulate in MS lesions. While they normally regulate tissue homeostasis and facilitate clearance neurotoxic molecules oxidized phosphatidylcholines (OxPCs), their transcriptome neuroprotective functions reprogrammed by aging. Thus, determining factors instigate aging microglia dysfunction can lead to new insights for promoting repair halting disease progression. Through single-cell RNA sequencing (scRNAseq), we identified Lgals3, which encodes galectin-3 (Gal3), as an age upregulated gene responding OxPC. Consistently, excess Gal3 accumulated OxPC lysolecithin-induced focal spinal cord white matter (SCWM) lesions middle-aged mice compared young mice. was also elevated mouse experimental autoimmune encephalomyelitis (EAE) more importantly brain from two male one female individuals. delivery alone into did not induce damage, its co-delivery increased cleaved caspase 3 IL-1β within exacerbated OxPC-induced injury. Conversely, OxPC-mediated neurodegeneration reduced Gal3-/- Gal3+/+ neuroinflammation overexpression microglia/macrophages may be detrimental CNS.SIGNIFICANCE STATEMENT accelerates such Understanding molecular mechanisms increases susceptibility damage could strategies manage Here, highlight microglia/macrophage-associated (Gal3) More importantly, co-injection lipids found lesions, caused greater injection alone, whereas genetic loss damage. These results demonstrate suggest deposition contribute neurodegeneration.

Язык: Английский

Insulin-degrading enzyme: Roles and pathways in ameliorating cognitive impairment associated with Alzheimer's disease and diabetes DOI Creative Commons

Yue Tian,

Guangchan Jing,

Mengren Zhang

и другие.

Ageing Research Reviews, Год журнала: 2023, Номер 90, С. 101999 - 101999

Опубликована: Июль 4, 2023

Accumulation of amyloid-β in the central nervous system is a common feature Alzheimer's disease (AD) and diabetes-related cognitive impairment. Since insulin-degrading enzyme (IDE) can break down plaques, there considerable interest using this to treat both neurological disorders. In review, we have summarized pre-clinical clinical research on potential application IDE for improvement Furthermore, presented an overview main pathways that be targeted mitigate progression AD impairment caused by diabetes.

Язык: Английский

Процитировано

27
Current views on meningeal lymphatics and immunity in aging and Alzheimer’s disease DOI Creative Commons
Shanon Rego, Guadalupe Sánchez, Sandro Dá Mesquita

и другие.

Molecular Neurodegeneration, Год журнала: 2023, Номер 18(1)

Опубликована: Авг. 14, 2023

Abstract Alzheimer’s disease (AD) is an aging-related form of dementia associated with the accumulation pathological aggregates amyloid beta and neurofibrillary tangles in brain. These phenomena are accompanied by exacerbated inflammation marked neuronal loss, which altogether contribute to accelerated cognitive decline. The multifactorial nature AD, allied our still limited knowledge its etiology pathophysiology, have lessened capacity develop effective treatments for AD patients. Over last few decades, genome wide association studies biomarker development, alongside mechanistic experiments involving animal models, identified different immune components that play key roles modulation brain pathology affecting progression severity. As we will relay this review, much recent efforts been directed better understanding role innate immunity, particularly microglia. However, despite lack diversity within resident cells, border tissues, especially meninges, harbour a considerable number types subtypes adaptive cells. Alongside microglia, taken centre stage as important players research, there new exciting evidence pointing namely T B cells found modulators neuroinflammation (dys)function AD. Importantly, genuine functional lymphatic vascular network present around outermost meningeal layer, dura. lymphatics directly connected peripheral system mammalian species, including humans, crucial preserving “healthy” surveillance CNS, shaping responses, not only locally at but also level tissue. In provide comprehensive view on current about vasculature, emphasizing described modulating CNS fluid macromolecule drainage, well glial function aging

Язык: Английский

Процитировано

27
Immune Regulatory Functions of Macrophages and Microglia in Central Nervous System Diseases DOI Open Access
Michael Poppell, Grace Hammel, Yi Ren

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(6), С. 5925 - 5925

Опубликована: Март 21, 2023

Macrophages can be characterized as a very multifunctional cell type with spectrum of phenotypes and functions being observed spatially temporally in various disease states. Ample studies have now demonstrated possible causal link between macrophage activation the development autoimmune disorders. How these cells may contributing to adaptive immune response potentially perpetuating progression neurodegenerative diseases neural injuries is not fully understood. Within this review, we hope illustrate role that macrophages microglia play initiators CNS by offering evidence of: (1) types responses processes antigen presentation each disease, (2) receptors involved macrophage/microglial phagocytosis disease-related debris or molecules, and, finally, (3) implications macrophages/microglia on pathogenesis diseases.

Язык: Английский

Процитировано

25
Maintenance of mitochondrial homeostasis for Alzheimer's disease: Strategies and challenges DOI Creative Commons
Ying Han,

Daozhou Liu,

Ying Cheng

и другие.

Redox Biology, Год журнала: 2023, Номер 63, С. 102734 - 102734

Опубликована: Май 6, 2023

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, and its early onset closely related to mitochondrial energy metabolism. The brain only 2% body weight, but consumes 20% total needs. Mitochondria are responsible for providing in cells, maintaining their homeostasis ensures an adequate supply brain. Mitochondrial constituted by quantity quality control, which dynamically regulated metabolism, dynamics control. Impaired metabolism cells occurs AD, a promising therapeutic target future. We summarized mechanism influence on pathogenesis strategies homeostasis, targeting strategies. This review concludes with authors' opinions future research development AD.

Язык: Английский

Процитировано

24
Elevated Galectin-3 Is Associated with Aging, Multiple Sclerosis, and Oxidized Phosphatidylcholine-Induced Neurodegeneration DOI Creative Commons

Sara Xue,

Brian Lozinski, Samira Ghorbani

и другие.

Journal of Neuroscience, Год журнала: 2023, Номер 43(25), С. 4725 - 4737

Опубликована: Май 19, 2023

Aging is a significant risk factor associated with the progression of CNS neurodegenerative diseases including multiple sclerosis (MS). Microglia, resident macrophages parenchyma, are major population immune cells that accumulate in MS lesions. While they normally regulate tissue homeostasis and facilitate clearance neurotoxic molecules oxidized phosphatidylcholines (OxPCs), their transcriptome neuroprotective functions reprogrammed by aging. Thus, determining factors instigate aging microglia dysfunction can lead to new insights for promoting repair halting disease progression. Through single-cell RNA sequencing (scRNAseq), we identified Lgals3, which encodes galectin-3 (Gal3), as an age upregulated gene responding OxPC. Consistently, excess Gal3 accumulated OxPC lysolecithin-induced focal spinal cord white matter (SCWM) lesions middle-aged mice compared young mice. was also elevated mouse experimental autoimmune encephalomyelitis (EAE) more importantly brain from two male one female individuals. delivery alone into did not induce damage, its co-delivery increased cleaved caspase 3 IL-1β within exacerbated OxPC-induced injury. Conversely, OxPC-mediated neurodegeneration reduced Gal3-/- Gal3+/+ neuroinflammation overexpression microglia/macrophages may be detrimental CNS.SIGNIFICANCE STATEMENT accelerates such Understanding molecular mechanisms increases susceptibility damage could strategies manage Here, highlight microglia/macrophage-associated (Gal3) More importantly, co-injection lipids found lesions, caused greater injection alone, whereas genetic loss damage. These results demonstrate suggest deposition contribute neurodegeneration.

Язык: Английский

Процитировано

24