scholarly journals Neurotoxicity of pre-incubated alpha-synuclein with neutral nanoliposomes on PC12 and SHSY5Y cell lines

2017 ◽  
Vol 0 (0) ◽  
pp. 0-0 ◽  
Author(s):  
Farhang Aliakbari ◽  
Ali. Akbar Shabani ◽  
Hassan Bardania ◽  
Hadieh Alsadat Eslampanah Seyedi ◽  
Hossein Mohammad-Beigi ◽  
...  
Keyword(s):  
Cell Lines ◽  
Alpha Synuclein ◽  
Shsy5y Cell

scholarly journals Gene-corrected p.A30P SNCA patient-derived isogenic neurons rescue neuronal branching and function

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Peter A. Barbuti ◽  
Jochen Ohnmacht ◽  
Bruno F. R. Santos ◽  
Paul M. Antony ◽  
François Massart ◽  
...  
Keyword(s):  
Cell Lines ◽  
Dopaminergic Neurons ◽  
Alpha Synuclein ◽  
Energy Deficit ◽  
Neuronal Function ◽  
Dominant Form ◽  
Transcriptional Alterations ◽  
Autosomal Dominant Form ◽  
And Function ◽  
First Time

AbstractParkinson’s disease (PD) is characterised by the degeneration of A9 dopaminergic neurons and the pathological accumulation of alpha-synuclein. The p.A30P SNCA mutation generates the pathogenic form of the alpha-synuclein protein causing an autosomal-dominant form of PD. There are limited studies assessing pathogenic SNCA mutations in patient-derived isogenic cell models. Here we provide a functional assessment of dopaminergic neurons derived from a patient harbouring the p.A30P SNCA mutation. Using two clonal gene-corrected isogenic cell lines we identified image-based phenotypes showing impaired neuritic processes. The pathological neurons displayed impaired neuronal activity, reduced mitochondrial respiration, an energy deficit, vulnerability to rotenone, and transcriptional alterations in lipid metabolism. Our data describes for the first time the mutation-only effect of the p.A30P SNCA mutation on neuronal function, supporting the use of isogenic cell lines in identifying image-based pathological phenotypes that can serve as an entry point for future disease-modifying compound screenings and drug discovery strategies.

scholarly journals Alpha-synuclein levels modulate seeding and aggregation in cultured cells

2021 ◽  
Author(s):  
Eftychia Vasili ◽  
Antonio Dominguez-Meijide ◽  
Manuel Flores-León ◽  
Mohammed Al-Azzani ◽  
Angeliki Kanellidi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Cultured Cells ◽  
Neurodegenerative Disorder ◽  
Alpha Synuclein ◽  
Lewy Neurites ◽  
Stable Cell Lines ◽  
The Impact

Abstract Background Parkinson's disease is a progressive neurodegenerative disorder characterized by the accumulation of misfolded alpha-synuclein in intraneuronal inclusions known as Lewy bodies and Lewy neurites. Multiple studies strongly implicate the levels of alpha-synuclein as a major risk factor for the onset and progression of Parkinson’s disease. alpha-Synuclein pathology spreads progressively throughout interconnected brain regions but the precise molecular mechanisms underlying alpha-synuclein spreading and accumulation remain obscure. Methods Here, using stable cell lines expressing alpha-synuclein, we examined the correlation between endogenous alpha-synuclein levels and the seeding propensity by exogenous alpha-synuclein pre-formed fibrils. We applied biochemical approaches and imaging methods in stable cell lines expressing alpha-synuclein and in primary neurons to determine the impact of alpha-synuclein expression levels on seeding and aggregation. Results Our results indicate that alpha-synuclein levels define the pattern and severity of aggregation and the extent of p-alpha-synuclein deposition, likely explaining the selective vulnerability of different cell types in synucleinopathies. Conclusions The elucidation of the cellular processes involved in the pathological aggregation of alpha-synuclein will enable the identification of novel targets and the development of therapeutic strategies for Parkinson's disease and other synucleinopathies.

scholarly journals LRRK2 kinase inhibitors reduce alpha-synuclein in human neuronal cell lines with the G2019S mutation

2020 ◽  
Vol 144 ◽  
pp. 105049
Author(s):  
Ye Zhao ◽  
Shikara Keshiya ◽  
Gayathri Perera ◽  
Lauren Schramko ◽  
Glenda M. Halliday ◽  
...  
Keyword(s):  
Cell Lines ◽  
Kinase Inhibitors ◽  
Neuronal Cell ◽  
Alpha Synuclein ◽  
Human Neuronal Cell ◽  
G2019s Mutation ◽  
Neuronal Cell Lines ◽  
Lrrk2 Kinase

scholarly journals Endogenous Levels of Alpha-Synuclein Modulate Seeding and Aggregation in Cultured Cells

2022 ◽  
Author(s):  
Eftychia Vasili ◽  
Antonio Dominguez-Meijide ◽  
Manuel Flores-León ◽  
Mohammed Al-Azzani ◽  
Angeliki Kanellidi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Cultured Cells ◽  
Neurodegenerative Disorder ◽  
Alpha Synuclein ◽  
Lewy Neurites ◽  
Stable Cell Lines ◽  
The Impact

AbstractParkinson’s disease is a progressive neurodegenerative disorder characterized by the accumulation of misfolded alpha-synuclein in intraneuronal inclusions known as Lewy bodies and Lewy neurites. Multiple studies strongly implicate the levels of alpha-synuclein as a major risk factor for the onset and progression of Parkinson’s disease. Alpha-synuclein pathology spreads progressively throughout interconnected brain regions but the precise molecular mechanisms underlying the seeding of alpha-synuclein aggregation are still unclear. Here, using stable cell lines expressing alpha-synuclein, we examined the correlation between endogenous alpha-synuclein levels and the seeding propensity by exogenous alpha-synuclein preformed fibrils. We applied biochemical approaches and imaging methods in stable cell lines expressing alpha-synuclein and in primary neurons to determine the impact of alpha-synuclein levels on seeding and aggregation. Our results indicate that the levels of alpha-synuclein define the pattern and severity of aggregation and the extent of p-alpha-synuclein deposition, likely explaining the selective vulnerability of different cell types in synucleinopathies. The elucidation of the cellular processes involved in the pathological aggregation of alpha-synuclein will enable the identification of novel targets and the development of therapeutic strategies for Parkinson’s disease and other synucleinopathies.

scholarly journals Hydrogen sulfide generation from L-cysteine in the human glioblastoma-astrocytoma U-87 MG and neuroblastoma SHSY5Y cell lines

2017 ◽  
Vol 64 (1) ◽  
Author(s):  
Maria Wróbel ◽  
Patrycja Bronowicka-Adamska ◽  
Anna Bentke
Keyword(s):  
Hydrogen Sulfide ◽  
Cell Lines ◽  
Neuroblastoma Cells ◽  
Hplc Method ◽  
Human Glioblastoma ◽  
Astrocytoma Cells ◽  
Shsy5y Cell ◽  
Mercaptopyruvate Sulfurtransferase ◽  
Catalyzed Reactions

Hydrogen sulfide (H2S) is endogenously synthesized from L-cysteine in reactions catalyzed by cystathionine beta-synthase (CBS, EC 4.2.1.22) and gamma-cystathionase (CSE, EC 4.4.1.1). The role of 3-mercaptopyruvate sulfurtransferase (MPST, EC 2.8.1.2) in H2S generation is also considered; it could be important for tissues with low CTH activity, e.g. cells of the nervous system. The expression and the activity of CBS, CTH, and MPST have been detected in the human glioblastoma-astrocytoma (U-87 MG) and neuroblastoma (SHSY5Y) cell lines. In both the cell lines, the expression and activity of MPST were the highest among the investigated enzymes, suggesting its possible role in the generation of H2S. The RP-HPLC method was used to determine cystathionine and alpha-ketobutyrate, products of the CBS and CTH-catalyzed reactions. A difference in cystathionine levels between cell homogenates with totally CTH-inhibiting concentrations of DL-propargylglycine and without the inhibitor was employed to evaluate the activity of CBS. A higher expression and the activities of the CBS, CTH, MPST in the neuroblastoma cells were associated with more an intensive generation of H2S in the presence of 2mM cysteine. A threefold higher level of sulfane sulfur, a potential source of hydrogen sulfide, was detected in the astrocytoma cells in comparison to the neuroblastoma cells.

scholarly journals Gene-corrected Parkinson’s disease neurons show the A30P alpha-synuclein point mutation leads to reduced neuronal branching and function

2020 ◽  
Author(s):  
Peter A. Barbuti ◽  
Bruno FR. Santos ◽  
Paul M. Antony ◽  
Francois Massart ◽  
Gérald Cruciani ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Lines ◽  
Dopaminergic Neurons ◽  
Cell Model ◽  
Control Cell ◽  
Electrode Array ◽  
Alpha Synuclein ◽  
Functionally Impaired ◽  
Mitochondrial Toxin

AbstractParkinson’s disease is characterised by the degeneration of A9 dopaminergic neurons and the pathological accumulation of alpha-synuclein. In a patient-derived stem cell model, we have generated dopaminergic neurons from an individual harbouring the p.A30P SNCA mutation and compared those neurons against gene-corrected isogenic control cell lines. We have used confocal microscopy to assess the neuronal network, specifically segmenting dopaminergic neurons and have identified image-based phenotypes showing axonal impairment and reduced neurite branching. We show using multi-electrode array (MEA) technology that the neurons carrying the endogenous p.A30P alpha-synuclein mutation are functionally impaired and identified mitochondrial dysfunction as a pathogenic cellular phenotype. We report that against gene-corrected isogenic control cell lines the neurons carrying the p.A30P SNCA mutation have a deficit and are susceptible to the mitochondrial toxin and environmental pesticide Rotenone. Our data supports the use of isogenic cell lines in identifying image-based pathological phenotypes that can serve as an entry point for future disease modifying compound screenings and drug discovery strategies.

scholarly journals Endogenous Levels of Alpha-synuclein Modulate Seeding and Aggregation in Cultured Cells

2021 ◽  
Author(s):  
Eftychia Vasili ◽  
Antonio Dominguez-Meijide ◽  
Manuel Flores-Léon ◽  
Mohammed Al-Azzani ◽  
Angeliki Kanellidi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Cultured Cells ◽  
Neurodegenerative Disorder ◽  
Alpha Synuclein ◽  
Lewy Neurites ◽  
Stable Cell Lines ◽  
The Impact

Abstract Background: Parkinson's disease is a progressive neurodegenerative disorder characterized by the accumulation of misfolded alpha-synuclein in intraneuronal inclusions known as Lewy bodies and Lewy neurites. Multiple studies strongly implicate the levels of alpha-synuclein as a major risk factor for the onset and progression of Parkinson’s disease. Alpha-synuclein pathology spreads progressively throughout interconnected brain regions but the precise molecular mechanisms underlying the seeding of alpha-synuclein aggregation are still unclear.Methods: Here, using stable cell lines expressing alpha-synuclein, we examined the correlation between endogenous alpha-synuclein levels and the seeding propensity by exogenous alpha-synuclein pre-formed fibrils. We applied biochemical approaches and imaging methods in stable cell lines expressing alpha-synuclein and in primary neurons to determine the impact of alpha-synuclein levels on seeding and aggregation. Results: Our results indicate that the levels of alpha-synuclein define the pattern and severity of aggregation and the extent of p-alpha-synuclein deposition, likely explaining the selective vulnerability of different cell types in synucleinopathies. Conclusions: The elucidation of the cellular processes involved in the pathological aggregation of alpha-synuclein will enable the identification of novel targets and the development of therapeutic strategies for Parkinson's disease and other synucleinopathies.

scholarly journals Investigation of cytotoxicity induced by Nigella sativa and Azadirachta indica using MDA-MB-231, HCT 116 and SHSY5Y cell lines

2017 ◽  
Vol 9 (2) ◽  
pp. 192-195 ◽  
Author(s):  
Sayani Banerjee ◽  
Shefali Pandey ◽  
Purbasha Mukherjee ◽  
Afia Sayeed ◽  
Apoorva Vasant Pandurangi ◽  
...  
Keyword(s):  
Cell Lines ◽  
Azadirachta Indica ◽  
Nigella Sativa ◽  
Shsy5y Cell ◽  
Hct 116
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