scholarly journals Age-Related Increase in Caveolin-1 Expression Facilitates Cell-to-Cell Transmission of α-Synuclein in Neurons

2021 ◽  
Author(s):  
Tae-Young Ha ◽  
Yu Ree Choi ◽  
Hye Rin Noh ◽  
Seon-Heui Cha ◽  
Jae-Bong Kim ◽  
...  
Keyword(s):  
Risk Factor ◽  
Inclusion Bodies ◽  
Aging Process ◽  
Caveolin 1 ◽  
Age Related ◽  
Cell Transmission ◽  
Tyrosine 14 ◽  
The Relationship ◽  
The Brain ◽  
Related Increase

Abstract Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, with aging being considered the greatest risk factor for developing PD. Caveolin-1 (Cav-1) is known to participate in the aging process. Recent evidence indicates that prion-like propagation of misfolded α-synuclein (α-syn) released from neurons to neighboring neurons plays an important role in PD progression. In the present study, we demonstrated that cav-1 expression in the brain increased with age, and considerably increased in the brain of A53T α-syn transgenic mice. Cav-1 overexpression facilitated the uptake of α-syn into neurons and formation of additional Lewy body-like inclusion bodies, phosphorylation of cav-1 at tyrosine 14 was found to be crucial for this process. This study demonstrates the relationship between age and α-syn spread and will facilitate our understanding of the molecular mechanism of the cell-to-cell transmission of α-syn.

scholarly journals Age-related increase in caveolin-1 expression facilitates cell-to-cell transmission of α-synuclein in neurons

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Tae-Young Ha ◽  
Yu Ree Choi ◽  
Hye Rin Noh ◽  
Seon-Heui Cha ◽  
Jae-Bong Kim ◽  
...  
Keyword(s):  
Risk Factor ◽  
Inclusion Bodies ◽  
Aging Process ◽  
Caveolin 1 ◽  
Age Related ◽  
Cell Transmission ◽  
Tyrosine 14 ◽  
The Relationship ◽  
The Brain ◽  
Related Increase

AbstractParkinson's disease (PD) is the second most prevalent neurodegenerative disease, with aging being considered the greatest risk factor for developing PD. Caveolin-1 (Cav-1) is known to participate in the aging process. Recent evidence indicates that prion-like propagation of misfolded α-synuclein (α-syn) released from neurons to neighboring neurons plays an important role in PD progression. In the present study, we demonstrated that cav-1 expression in the brain increased with age, and considerably increased in the brain of A53T α-syn transgenic mice. Cav-1 overexpression facilitated the uptake of α-syn into neurons and formation of additional Lewy body-like inclusion bodies, phosphorylation of cav-1 at tyrosine 14 was found to be crucial for this process. This study demonstrates the relationship between age and α-syn spread and will facilitate our understanding of the molecular mechanism of the cell-to-cell transmission of α-syn.

scholarly journals Age-related increase in caveolin-1 expression facilitates cell-to-cell transmission of α-synuclein in neurons

2020 ◽  
Author(s):  
Tae-Young Ha ◽  
Yu Ree Choi ◽  
Hye Rin Noh ◽  
Seon-Heui Cha ◽  
Jae-Bong Kim ◽  
...  
Keyword(s):  
Lewy Body ◽  
Inclusion Bodies ◽  
Primary Neurons ◽  
Caveolin 1 ◽  
Age Related ◽  
Microfluidic Chamber ◽  
Cell Transmission ◽  
Tyrosine 14 ◽  
The Relationship ◽  
The Brain

Abstract Background: Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, with aging being considered the greatest risk factor for developing PD. Caveolin-1 (Cav-1) is known to participate in the aging process. Recent evidence indicates that prion-like propagation of misfolded α-synuclein (α-syn) released from neurons to neighboring neurons plays an important role in PD progression. In the present study, we explored the association between cav-1 and cell-to-cell transmission of α-syn.Methods: Using SH-SY5Y cells and primary neurons overexpressing WT and Y14A cav-1, we investigated the effect of cav-1 expression on the uptake of α-syn using a dual chamber system. Additionally, we investigated the effect of cav-1 expression on the formation of Lewy body-like inclusions using co-culture assay and microfluidic chamber assay.Results: We demonstrated that cav-1 expression in the brain increased with age, and considerably increased in the brain of A53T α-syn transgenic mice. Cav-1 overexpression facilitated the uptake of α-syn into neurons and formation of additional Lewy body-like inclusion bodies, phosphorylation of cav-1 at tyrosine 14 was found to be crucial for this process. Conclusions: This study demonstrates the relationship between age and α-syn spread and will facilitate our understanding of the molecular mechanism of the cell-to-cell transmission of α-syn.

scholarly journals Age-Related Increase in Caveolin-1 Expression Facilitates Cell-To-Cell Transmission of α-Synuclein in Neurons

2020 ◽  
Author(s):  
Tae-Young Ha ◽  
Yu Ree Choi ◽  
Hye Rin Noh ◽  
Seon-Heui Cha ◽  
Jae-Bong Kim ◽  
...  
Keyword(s):  
Lewy Body ◽  
Inclusion Bodies ◽  
Primary Neurons ◽  
Caveolin 1 ◽  
Age Related ◽  
Microfluidic Chamber ◽  
Cell Transmission ◽  
Tyrosine 14 ◽  
The Relationship ◽  
The Brain

Abstract Background: Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, with aging being considered the greatest risk factor for developing PD. Caveolin-1 (Cav-1) is known to participate in the aging process. Recent evidence indicates that prion-like propagation of misfolded α-synuclein (α-syn) released from neurons to neighboring neurons plays an important role in PD progression. In the present study, we explored the association between cav-1 and cell-to-cell transmission of α-syn.Methods: Using SH-SY5Y cells and primary neurons overexpressing WT and Y14A cav-1, we investigated the effect of cav-1 expression on the uptake of α-syn using a dual chamber system. Additionally, we investigated the effect of cav-1 expression on the formation of Lewy body-like inclusions using co-culture assay and microfluidic chamber assay.Results: We demonstrated that cav-1 expression in the brain increased with age, and considerably increased in the brain of A53T α-syn transgenic mice. Cav-1 overexpression facilitated the uptake of α-syn into neurons and formation of additional Lewy body-like inclusion bodies, phosphorylation of cav-1 at tyrosine 14 was found to be crucial for this process. Conclusions: This study demonstrates the relationship between age and α-syn spread and will facilitate our understanding of the molecular mechanism of the cell-to-cell transmission of α-syn.

scholarly journals Age-related increase in caveolin-1 expression facilitates cell-to-cell transmission of α-synuclein in neurons

2021 ◽  
Author(s):  
Tae-Young Ha ◽  
Yu Ree Choi ◽  
Hye Rin Noh ◽  
Seon-Heui Cha ◽  
Jae-Bong Kim ◽  
...  
Keyword(s):  
Lewy Body ◽  
Inclusion Bodies ◽  
Primary Neurons ◽  
Caveolin 1 ◽  
Age Related ◽  
Microfluidic Chamber ◽  
Cell Transmission ◽  
Tyrosine 14 ◽  
The Relationship ◽  
The Brain

Abstract Background: Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, with aging being considered the greatest risk factor for developing PD. Caveolin-1 (Cav-1) is known to participate in the aging process. Recent evidence indicates that prion-like propagation of misfolded α-synuclein (α-syn) released from neurons to neighboring neurons plays an important role in PD progression. In the present study, we explored the association between cav-1 and cell-to-cell transmission of α-syn.Methods: Using SH-SY5Y cells and primary neurons overexpressing WT and Y14A cav-1, we investigated the effect of cav-1 expression on the uptake of α-syn using a dual chamber system. Additionally, we investigated the effect of cav-1 expression on the formation of Lewy body-like inclusions using co-culture assay and microfluidic chamber assay.Results: We demonstrated that cav-1 expression in the brain increased with age, and considerably increased in the brain of A53T α-syn transgenic mice. Cav-1 overexpression facilitated the uptake of α-syn into neurons and formation of additional Lewy body-like inclusion bodies, phosphorylation of cav-1 at tyrosine 14 was found to be crucial for this process. Conclusions: This study demonstrates the relationship between age and α-syn spread and will facilitate our understanding of the molecular mechanism of the cell-to-cell transmission of α-syn.

scholarly journals Phosphocaveolin-1 is a mechanotransducer that induces caveola biogenesis via Egr1 transcriptional regulation

2012 ◽  
Vol 199 (3) ◽  
pp. 425-435 ◽  
Author(s):  
Bharat Joshi ◽  
Michele Bastiani ◽  
Scott S. Strugnell ◽  
Cecile Boscher ◽  
Robert G. Parton ◽  
...  
Keyword(s):  
Carcinoma Cells ◽  
Caveolin 1 ◽  
Early Growth Response ◽  
Breast Carcinoma Cells ◽  
Transcriptional Inhibition ◽  
Kinase C ◽  
Tyrosine 14 ◽  
Regulatory Loop ◽  
Early Growth Response 1 ◽  
The Relationship

Caveolin-1 (Cav1) is an essential component of caveolae whose Src kinase-dependent phosphorylation on tyrosine 14 (Y14) is associated with regulation of focal adhesion dynamics. However, the relationship between these disparate functions remains to be elucidated. Caveola biogenesis requires expression of both Cav1 and cavin-1, but Cav1Y14 phosphorylation is dispensable. In this paper, we show that Cav1 tyrosine phosphorylation induces caveola biogenesis via actin-dependent mechanotransduction and inactivation of the Egr1 (early growth response-1) transcription factor, relieving inhibition of endogenous Cav1 and cavin-1 genes. Cav1 phosphorylation reduces Egr1 binding to Cav1 and cavin-1 promoters and stimulates their activity. In MDA-231 breast carcinoma cells that express elevated levels of Cav1 and caveolae, Egr1 regulated Cav1, and cavin-1 promoter activity was dependent on actin, Cav1, Src, and Rho-associated kinase as well as downstream protein kinase C (PKC) signaling. pCav1 is therefore a mechanotransducer that acts via PKC to relieve Egr1 transcriptional inhibition of Cav1 and cavin-1, defining a novel feedback regulatory loop to regulate caveola biogenesis.

scholarly journals Aging triggers an upregulation of a multitude of cytokines in the male and especially the female rodent hippocampus but more discrete changes in other brain regions

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Latarsha Porcher ◽  
Sophie Bruckmeier ◽  
Steven D. Burbano ◽  
Julie E. Finnell ◽  
Nicole Gorny ◽  
...  
Keyword(s):  
Statistical Tests ◽  
Ventral Hippocampus ◽  
Brain Regions ◽  
Cytokine Expression ◽  
Brown Norway ◽  
Mouse Strains ◽  
Gm Csf ◽  
Age Related ◽  
The Brain ◽  
Related Increase

Abstract Background Despite widespread acceptance that neuroinflammation contributes to age-related cognitive decline, studies comparing protein expression of cytokines in the young versus old brains are surprisingly limited in terms of the number of cytokines and brain regions studied. Complicating matters, discrepancies abound—particularly for interleukin 6 (IL-6)—possibly due to differences in sex, species/strain, and/or the brain regions studied. Methods As such, we clarified how cytokine expression changes with age by using a Bioplex and Western blot to measure multiple cytokines across several brain regions of both sexes, using 2 mouse strains bred in-house as well as rats obtained from NIA. Parametric and nonparametric statistical tests were used as appropriate. Results In the ventral hippocampus of C57BL/6J mice, we found age-related increases in IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-6, IL-9, IL-10, IL-12p40, IL-12p70, IL-13, IL-17, eotaxin, G-CSF, interfeuron δ, KC, MIP-1a, MIP-1b, rantes, and TNFα that are generally more pronounced in females, but no age-related change in IL-5, MCP-1, or GM-CSF. We also find aging is uniquely associated with the emergence of a module (a.k.a. network) of 11 strongly intercorrelated cytokines, as well as an age-related shift from glycosylated to unglycosylated isoforms of IL-10 and IL-1β in the ventral hippocampus. Interestingly, age-related increases in extra-hippocampal cytokine expression are more discreet, with the prefrontal cortex, striatum, and cerebellum of male and female C57BL/6J mice demonstrating robust age-related increase in IL-6 expression but not IL-1β. Importantly, we found this widespread age-related increase in IL-6 also occurs in BALB/cJ mice and Brown Norway rats, demonstrating conservation across species and rearing environments. Conclusions Thus, age-related increases in cytokines are more pronounced in the hippocampus compared to other brain regions and can be more pronounced in females versus males depending on the brain region, genetic background, and cytokine examined.

scholarly journals Metformin Alleviates Obesity and Systemic Oxidative Stress in Obese Young Swine

2020 ◽  
Vol 13 (7) ◽  
pp. 142
Author(s):  
Susana Astiz ◽  
Antonio Gonzalez-Bulnes ◽  
Isabel Astiz ◽  
Alicia Barbero ◽  
Jose Luis Pesantez-Pacheco ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Status ◽  
Swine Model ◽  
Oxygen Species ◽  
Systemic Oxidative Stress ◽  
Age Related ◽  
Cardiometabolic Disorders ◽  
Iberian Pig ◽  
The Relationship ◽  
Related Increase

The present study assessed the relationship between obesity induced by lifestyle and systemic oxidative stress and possible modulations by oral metformin treatments in young individuals, by using a translational swine model of obesity and associated cardiometabolic disorders (Iberian pig). The results indicate the existence of an age-related increase in both adiposity and systemic oxidative stress (using hydrogen peroxide as a marker), which is higher in individuals with obesogenic lifestyle and increased weight and obesity. Such effect was not found in individuals treated with metformin. The translation of these results suggests that childhood obesity increases production of reactive oxygen species (ROS), and therefore systemic oxidative stress. Treatment with metformin would improve such oxidative status.

scholarly journals Age related increase in cav-1 expression facilitates cell-to-cell transmission of α-synuclein in neurons

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S105
Author(s):  
Tae-Young Ha ◽  
Yu Ree Choi ◽  
Hye Rin Noh ◽  
Ka Young Kim ◽  
Sang Myun Park
Keyword(s):  
Age Related ◽  
Cell Transmission ◽  
Related Increase

scholarly journals A Walnut-Enriched Diet Modifies the Oxylipin Profile in Liver and Brain of Aged Mice — Impact on Inflammation Markers

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1203-1203
Author(s):  
Gunter Eckert ◽  
Gunter Esselun ◽  
Elisabeth Koch ◽  
Nils Schebb
Keyword(s):  
Physical Activity ◽  
Fatty Acids ◽  
Brain Aging ◽  
Inflammatory Marker ◽  
Inflammation Markers ◽  
Aged Mice ◽  
Funding Sources ◽  
Age Related ◽  
The Brain ◽  
Related Increase

Abstract Objectives Neuroinflammation contributes to brain-aging which may be mitigated by anti-inflammatory oxylipins. Based on our previous findings that a 6% walnut-enriched diet alone, and additional physical activity (PA), enhanced cognition in 18 months old NMRI, we now investigated the effects of this diet on oxylipin- and inflammatory marker levels in liver and brain. Methods 18 months and 3 months old female NMRI mice were fed with a 6% walnut-enriched diet. Oxylipins were determined in brain and liver sections using LC-MS. Expression of IL1β gene was determined by qRT-PCR. Results The walnut diet compensates for the age related increase in IL1β gene expression in the liver of mice, whereas expression in the brain was not affected. Basal levels of oxylipins in brain and liver samples isolated from young mice were generally lower compared to aged mice. The walnut diet further increased oxylipin levels of walnut specific fatty acids in liver and brain of aged mice. Enrichment of linoleic acid (LA) and α-linolenic acid (ALA) derived oxylipin levels were quantitatively higher in the liver compared to the brain (P < 0.0001). Hydroxy-oxylipins (HO) based on fatty acid LA were significantly increased in brain (P < 0.001) and liver (P < 0.0001) compared to control mice, while ALA based HO were only detected in the brains of walnut fed mice. The walnut diet in combination with physical activity (PA) reduced ARA based oxylipin levels (P < 0.05). Across all groups, concentrations of prostanoids were higher in the brain as compared to liver (P < 0.001). In the liver, walnuts tended to decrease PGD2 and TxB2 levels while increasing 6-keto PGF1α. The latter, as well as TxB2 tended to be decreased in the brain. Other ARA based prostanoids were unaffected. Effects of PA were contrary to each other, tending to increase ARA based prostanoids in the liver while decreasing them in the brain. PA further enhanced this effect in the brain, but tended to increase the inflammatory response in the liver. Conclusions A walnut diet differentially affects the oxylipin profile of liver and brain in aged mice. Production of oxylipins based on walnut fatty acids is generally increased. Attenuation of age-related, chronic inflammation in might be one of walnut's benefits and may contribute to a healthier aging of the brain. Funding Sources Research was supported by grants from California Walnut Commission.

scholarly journals Melatonin, aging, and COVID-19: Could melatonin be beneficial for COVID-19 treatment in the elderly?

2020 ◽  
Vol 50 (6) ◽  
pp. 1504-1512
Author(s):  
Güler ÖZTÜRK ◽  
Kazime Gonca AKBULUT ◽  
Şevin GÜNEY
Keyword(s):  
Aging Process ◽  
Biological Process ◽  
The Elderly ◽  
The Body ◽  
Biological Processes ◽  
Therapeutic Approaches ◽  
Free Radical Reactions ◽  
Age Related ◽  
The Relationship ◽  
Age Related Changes

The aim of this review is to summarize current studies on the relationship between melatonin and aging. Nowadays, age-related diseases come into prominence, and identifying age-related changes and developing proper therapeutic approaches are counted as some of the major issues regarding community health. Melatonin is the main hormone of the pineal gland. Melatonin is known to influence many biological processes in the body, including circadian rhythms, the immune system, and neuroendocrine and cardiovascular functions.Melatoninrhythms also reflect the biological process of aging. Aging is an extremely complex and multifactorial process. Melatonin levels decline considerably with aging and its decline is associated with several age-related diseases. Aging is closely associated with oxidative damage and mitochondrial dysfunction. Free radical reactions initiated by the mitochondria constitute the inherent aging process. Melatonin plays a pivotal role in preventing age-related oxidative stress. Coronavirus disease 2019 (COVID-19) fatality rates increase with chronic diseases and age, where melatonin levels decrease. For this reason, melatonin supplementation in elderly could be beneficial in COVID-19 treatment. Therefore, studies on the usage of melatonin in COVID-19 treatment are needed.

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