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Brain disposition of α-Synuclein: roles of brain barrier systems and implications for Parkinson's disease.

Bates CA, Zheng W - Fluids Barriers CNS (2014)

Bottom Line: The blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF) barriers (BCSFB) are responsible for regulating the access of nutrients and other molecules to the brain, but very little is known about their regulatory roles in maintaining the homeostasis of a-Syn in the CSF and brain parenchyma.This review analyzes the current literature reports on the transport of a-Syn by various brain cell types with a particular focus on the potential transport mechanisms of a-Syn at the BBB and BCSFB.The indication of altered a-Syn transport by brain barriers in PD pathoetiology and the perspectives in this research area are also discussed.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Health Sciences, Purdue University, 550 Stadium Mall Drive, HAMP 1173, West Lafayette, IN 47907, USA.

ABSTRACT
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the accumulation of α-Synuclein (a-Syn) into Lewy body inclusions and the loss of dopaminergic neurons in the substantia nigra (SN). Accumulation of a-Syn can induce a progressive, cyclical pathology that results in the transmission of toxic, aggregated a-Syn species to healthy neurons, leading to further neurodegeneration such as occurs in PD. The blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF) barriers (BCSFB) are responsible for regulating the access of nutrients and other molecules to the brain, but very little is known about their regulatory roles in maintaining the homeostasis of a-Syn in the CSF and brain parenchyma. This review analyzes the current literature reports on the transport of a-Syn by various brain cell types with a particular focus on the potential transport mechanisms of a-Syn at the BBB and BCSFB. The indication of altered a-Syn transport by brain barriers in PD pathoetiology and the perspectives in this research area are also discussed.

No MeSH data available.


Related in: MedlinePlus

Expression of α-Synuclein and clathrin in Z310 cells with or without a-Syn treatment in a typical experiment (n = 5). Z310 cells are immortalized rat choroidal epithelial cells established in this laboratory [47]. The cells were treated with or without 0.5 μM recombinant human a-Syn for 5 hours prior to immunostaining with the primary antibodies, followed by fluorescent secondary antibodies. Fluorescent signals for a-Syn and clathrin are shown in green and red, respectively. Merged images show a co-localization of a-Syn signals with those of clathrin.
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Figure 2: Expression of α-Synuclein and clathrin in Z310 cells with or without a-Syn treatment in a typical experiment (n = 5). Z310 cells are immortalized rat choroidal epithelial cells established in this laboratory [47]. The cells were treated with or without 0.5 μM recombinant human a-Syn for 5 hours prior to immunostaining with the primary antibodies, followed by fluorescent secondary antibodies. Fluorescent signals for a-Syn and clathrin are shown in green and red, respectively. Merged images show a co-localization of a-Syn signals with those of clathrin.

Mentions: Recent data from this laboratory have identified the presence of the mRNA encoding a-Syn as well as a-Syn proteins in choroid plexus tissue collected from rats; similar expression of a-Syn was also found in rat choroidal primary cells as well as in an immortalized rat choroid epithelial Z310 cell line (Figure 2) [45,46]. We suspect that this expression of a-Syn may play a role in a-Syn pathology and contribute to the development of a-Syn aggregates. Similar to the pathological pathway in astrocytes, the BCSFB may attempt to clear a-Syn aggregates from the CSF via the uptake of these polymers, which provides an opportunity for these polymers to interact with endogenous a-Syn in cells of the BCSFB and promote cell stress and accelerated a-Syn pathology.


Brain disposition of α-Synuclein: roles of brain barrier systems and implications for Parkinson's disease.

Bates CA, Zheng W - Fluids Barriers CNS (2014)

Expression of α-Synuclein and clathrin in Z310 cells with or without a-Syn treatment in a typical experiment (n = 5). Z310 cells are immortalized rat choroidal epithelial cells established in this laboratory [47]. The cells were treated with or without 0.5 μM recombinant human a-Syn for 5 hours prior to immunostaining with the primary antibodies, followed by fluorescent secondary antibodies. Fluorescent signals for a-Syn and clathrin are shown in green and red, respectively. Merged images show a co-localization of a-Syn signals with those of clathrin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4120720&req=5

Figure 2: Expression of α-Synuclein and clathrin in Z310 cells with or without a-Syn treatment in a typical experiment (n = 5). Z310 cells are immortalized rat choroidal epithelial cells established in this laboratory [47]. The cells were treated with or without 0.5 μM recombinant human a-Syn for 5 hours prior to immunostaining with the primary antibodies, followed by fluorescent secondary antibodies. Fluorescent signals for a-Syn and clathrin are shown in green and red, respectively. Merged images show a co-localization of a-Syn signals with those of clathrin.
Mentions: Recent data from this laboratory have identified the presence of the mRNA encoding a-Syn as well as a-Syn proteins in choroid plexus tissue collected from rats; similar expression of a-Syn was also found in rat choroidal primary cells as well as in an immortalized rat choroid epithelial Z310 cell line (Figure 2) [45,46]. We suspect that this expression of a-Syn may play a role in a-Syn pathology and contribute to the development of a-Syn aggregates. Similar to the pathological pathway in astrocytes, the BCSFB may attempt to clear a-Syn aggregates from the CSF via the uptake of these polymers, which provides an opportunity for these polymers to interact with endogenous a-Syn in cells of the BCSFB and promote cell stress and accelerated a-Syn pathology.

Bottom Line: The blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF) barriers (BCSFB) are responsible for regulating the access of nutrients and other molecules to the brain, but very little is known about their regulatory roles in maintaining the homeostasis of a-Syn in the CSF and brain parenchyma.This review analyzes the current literature reports on the transport of a-Syn by various brain cell types with a particular focus on the potential transport mechanisms of a-Syn at the BBB and BCSFB.The indication of altered a-Syn transport by brain barriers in PD pathoetiology and the perspectives in this research area are also discussed.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Health Sciences, Purdue University, 550 Stadium Mall Drive, HAMP 1173, West Lafayette, IN 47907, USA.

ABSTRACT
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the accumulation of α-Synuclein (a-Syn) into Lewy body inclusions and the loss of dopaminergic neurons in the substantia nigra (SN). Accumulation of a-Syn can induce a progressive, cyclical pathology that results in the transmission of toxic, aggregated a-Syn species to healthy neurons, leading to further neurodegeneration such as occurs in PD. The blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF) barriers (BCSFB) are responsible for regulating the access of nutrients and other molecules to the brain, but very little is known about their regulatory roles in maintaining the homeostasis of a-Syn in the CSF and brain parenchyma. This review analyzes the current literature reports on the transport of a-Syn by various brain cell types with a particular focus on the potential transport mechanisms of a-Syn at the BBB and BCSFB. The indication of altered a-Syn transport by brain barriers in PD pathoetiology and the perspectives in this research area are also discussed.

No MeSH data available.


Related in: MedlinePlus