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 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 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 Socioeconomic status moderates age-related differences in the brain’s functional network organization and anatomy across the adult lifespan

2018 ◽  
Vol 115 (22) ◽  
pp. E5144-E5153 ◽  
Author(s):  
Micaela Y. Chan ◽  
Jinkyung Na ◽  
Phillip F. Agres ◽  
Neil K. Savalia ◽  
Denise C. Park ◽  
...  
Keyword(s):  
Socioeconomic Status ◽  
Protective Factor ◽  
Middle Age ◽  
Functional Network ◽  
Brain Anatomy ◽  
Network Organization ◽  
Age Related ◽  
Wide Range ◽  
The Relationship ◽  
The Brain

An individual’s environmental surroundings interact with the development and maturation of their brain. An important aspect of an individual’s environment is his or her socioeconomic status (SES), which estimates access to material resources and social prestige. Previous characterizations of the relation between SES and the brain have primarily focused on earlier or later epochs of the lifespan (i.e., childhood, older age). We broaden this work to examine the relationship between SES and the brain across a wide range of human adulthood (20–89 years), including individuals from the less studied middle-age range. SES, defined by education attainment and occupational socioeconomic characteristics, moderates previously reported age-related differences in the brain’s functional network organization and whole-brain cortical structure. Across middle age (35–64 years), lower SES is associated with reduced resting-state system segregation (a measure of effective functional network organization). A similar but less robust relationship exists between SES and age with respect to brain anatomy: Lower SES is associated with reduced cortical gray matter thickness in middle age. Conversely, younger and older adulthood do not exhibit consistent SES-related difference in the brain measures. The SES–brain relationships persist after controlling for measures of physical and mental health, cognitive ability, and participant demographics. Critically, an individual’s childhood SES cannot account for the relationship between their current SES and functional network organization. These findings provide evidence that SES relates to the brain’s functional network organization and anatomy across adult middle age, and that higher SES may be a protective factor against age-related brain decline.

scholarly journals Assessment of the Potential Role of Tryptophan as the Precursor of Serotonin and Melatonin for the Aged Sleep-wake Cycle and Immune Function: Streptopelia Risoria as a Model

2009 ◽  
Vol 2 ◽  
pp. IJTR.S1129 ◽  
Author(s):  
Sergio D. Paredes ◽  
Carmen Barriga ◽  
Russel J. Reiter ◽  
Ana B. Rodríguez
Keyword(s):  
Immune Response ◽  
Potential Role ◽  
Suitable Model ◽  
Streptopelia Risoria ◽  
Age Related ◽  
Amino Acid Tryptophan ◽  
The Relationship ◽  
The Brain ◽  
Circulating Levels

In the present review we summarize the relationship between the amino acid, tryptophan, the neurotransmitter, serotonin, and the indole, melatonin, with the rhythms of sleep/wake and the immune response along with the possible connections between the alterations in these rhythms due to aging and the so-called “serotonin and melatonin deficiency state.” The decrease associated with aging of the brain and circulating levels of serotonin and melatonin seemingly contributes to the alterations of both the sleep/wake cycle and the immune response that typically accompany old age. The supplemental administration of tryptophan, e.g. the inclusion of tryptophan-enriched food in the diet, might help to remediate these age-related alterations due to its capacity of raise the serotonin and melatonin levels in the brain and blood. Herein, we also summarize a set of studies related to the potential role that tryptophan, and its derived product melatonin, may play in the restoration of the aged circadian rhythms of sleep/wake and immune response, taking the ringdove ( Streptopelia risoria) as a suitable model.

Spindle shaped bodies in foveolar cones of the baboon retina

1989 ◽  
Vol 47 ◽  
pp. 960-961
Author(s):  
W. Krebs ◽  
I. Krebs
Keyword(s):  
Cross Sections ◽  
Inclusion Bodies ◽  
Photoreceptor Cells ◽  
Papio Anubis ◽  
Retinal Photoreceptor ◽  
Age Related ◽  
Cone Cells ◽  
Membrane Bound ◽  
Oriented Parallel ◽  
Shaped Inclusion

Various inclusion bodies occur in vertebrate retinal photoreceptor cells. Most of them are membrane bound and associated with phagocytosis or they are age related residual bodies. We found an additional inclusion body in foveal cone cells of the baboon (Papio anubis) retina.The eyes of a 15 year old baboon were fixed by immersion in cacodylate buffered glutaraldehyde (2%)/formaldehyde (2%) as described in detail elsewhere . Pieces of retina from various locations, including the fovea, were embedded in epoxy resin such that radial or tangential sections could be cut.Spindle shaped inclusion bodies were found in the cytoplasm of only foveal cones. They were abundant in the inner segments, close to the external limiting membrane (Fig. 1). But they also occurred in the outer fibers, the perikarya, and the inner fibers (Henle’s fibers) of the cone cells. The bodies were between 0.5 and 2 μm long. Their central diameter was 0.2 to 0. 3 μm. They always were oriented parallel to the long axis of the cone cells. In longitudinal sections (Figs. 2,3) they seemed to have a fibrous skeleton that, in cross sections, turned out to consist of plate-like (Fig.4) and tubular profiles (Fig. 5).

Cognitive Factors Mediate the Relation Between Age and Flight Path Maintenance in General Aviation

2016 ◽  
Vol 6 (2) ◽  
pp. 81-90 ◽  
Author(s):  
Kathleen Van Benthem ◽  
Chris M. Herdman
Keyword(s):  
Cognitive Functioning ◽  
Flight Path ◽  
General Aviation ◽  
Cognitive Factors ◽  
Pilot Performance ◽  
Pilot Error ◽  
Age Related ◽  
And Performance ◽  
Relationship Of ◽  
The Relationship

Abstract. Identifying pilot attributes associated with risk is important, especially in general aviation where pilot error is implicated in most accidents. This research examined the relationship of pilot age, expertise, and cognitive functioning to deviations from an ideal circuit trajectory. In all, 54 pilots, of varying age, flew a Cessna 172 simulator. Cognitive measures were obtained using the CogScreen-AE ( Kay, 1995 ). Older age and lower levels of expertise and cognitive functioning were associated with significantly greater flight path deviations. The relationship between age and performance was fully mediated by a cluster of cognitive factors: speed and working memory, visual attention, and cognitive flexibility. These findings add to the literature showing that age-related changes in cognition may impact pilot performance.

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