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Papers by Marie-christine Galas

Journal of Biological Chemistry, 2010

Tau-mediated DNA protection in postmitotic neurons. Shown is a scheme illustrating the nuclear Ta... more Tau-mediated DNA protection in postmitotic neurons. Shown is a scheme illustrating the nuclear Tau protection of DNA integrity in heat-stressed neurons.

Additional file 12 : Figure S12. List of oligonucleotides used in mtDNA analysis and in BER assays.

Additional file 9 : Figure S9. PCR-based mtDNA damage analysis. (A) MtDNA damage analysis from 6-... more Additional file 9 : Figure S9. PCR-based mtDNA damage analysis. (A) MtDNA damage analysis from 6-mo Wt (n = 5) and Tg (n = 6) mice CA1 region by long range PCR. (B) MtDNA analysis of 12-mo Wt (n = 5) and Tg (n = 5) mice hippocampi. Data are presented as mean ± SEM. Statistics were performed with unpaired two-tailed Mann-Whitney test (**P

Additional file 8 : Figure S8. Increased mitochondrial Polβ in Tg mice hippocampal neurons. Repre... more Additional file 8 : Figure S8. Increased mitochondrial Polβ in Tg mice hippocampal neurons. Representative immunoelectron microscopy images of CA1 sections from 6-mo Tg and Wt mice hippocampus. The sections were labeled with Polβ antibodies (n = 3 for each mouse category). The scale bars represent 100 nm. Red arrows point Polβ localization

Additional file 7 : Figure S7. Absence of cytoplasmic accumulation of Polβ in 12-mo Tg mice hippo... more Additional file 7 : Figure S7. Absence of cytoplasmic accumulation of Polβ in 12-mo Tg mice hippocampal neurons. Representative images of sagittal CA1 sections from 12-mo Wt and Tg mice hippocampi. The sections were co-labeled with anti-phospho-tau (AT8), and Polβ antibodies (n = 3 for each mouse category). Immunofluorescence signals were analyzed using laser scanning confocal microscopy (z projection). Nuclei were detected with DAPI staining. Representative nuclei are delimitated by white dashed lines. The scale bars represent 20 μm. The intensity of the cellular and nuclear Polβ fluorescence signals was quantified within CA1 cells from 12-mo Wt and Tg hippocampi (nuclei: Wt, n = 84; Tg, n = 66; cellular: Wt, n = 97; Tg, n = 98). Graph shows the mean of nuclear fluorescence per mouse category. Data are presented as mean ± SEM.

Additional file 5 : Figure S5. BER activity is not changed in 12-mo Tg mice. Biochemical analysis... more Additional file 5 : Figure S5. BER activity is not changed in 12-mo Tg mice. Biochemical analysis of BER activity in hippocampal extracts from 12-mo Tg and Wt mice. (A) AP-site incision activity. Recombinant APE1 protein was used as a positive control. (B) Uracil removal activity. Purified recombinant UNG was used as a positive control. (C) 8-oxo-G removal activity Formamidopyrimidine DNA glycosylase (FPG) was used as a positive control. (D) Polβ nucleotide incorporation activity. (E) Quantifications of A-D, data are presented as mean ± SEM.

Additional file 2 : Figure S2. Tau pathology does not affect the expression of the key regulator ... more Additional file 2 : Figure S2. Tau pathology does not affect the expression of the key regulator of mitochondrial biogenesis Pgc1α. WB analysis of extracts from 6-mo Wt and Tg mice CA1 (Wt, n = 6; Tg, n = 5) (A), and from 12-mo Wt and Tg mice hippocampi (Wt, n = 5; Tg, n = 6) (B) for PGC-1α. Actin was used as loading control. Data are presented as mean ± SEM.

Additional file 1 : Figure S1. Tau pathology does not affect mitochondrial mass in CA1 neurons. W... more Additional file 1 : Figure S1. Tau pathology does not affect mitochondrial mass in CA1 neurons. WB analysis of extracts from 6-mo Wt and Tg mice CA1 (Wt, n = 6; Tg, n = 5) (A), and from 12-mo Wt and Tg mice hippocampi (Wt, n = 5; Tg, n = 6) (B) for VDAC1. Actin was used as loading control. Data are presented as mean ± SEM.

Calcium-binding proteins such as calretinin are abundantly expressed in distinctive patterns in t... more Calcium-binding proteins such as calretinin are abundantly expressed in distinctive patterns in the CNS, but their physiological function remains poorly understood. Calretinin is expressed in cerebellar granule cells, which provide the major excitatory input to Purkinje cells through parallel fibers. Calretinin-deficient mice exhibit dramatic alterations in motor coordination and Purkinje cell firing recorded in vivo through unknown mechanisms. In the present study, we used patch-clamp recording techniques in acute slice preparation to investigate the effect of a null mutation of the calretinin gene on the intrinsic electroresponsiveness of cerebellar granule cells at a mature developmental stage. Calretinin-deficient granule cells exhibit faster action potentials and generate repetitive spike discharge showing an enhanced frequency increase with injected currents. These alterations disappear when 0.15 mM of the exogenous fast-calcium buffer BAPTA is infused in the cytosol to restor...

Journal of Alzheimer's Disease, 2019

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases, characteriz... more Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases, characterized by the accumulation of extracellular amyloid plaques and intraneuronal neurofibrillary tangles. These tangles mainly consist of hyperphosphorylated tau protein. As it induces tau hyperphosphorylation in vitro and in vivo, hypothermia is a useful tool for screening potential neuroprotective compounds that ameliorate tau pathology. In this study, we examined the effect of prolactin-releasing peptide (PrRP), its lipidized analog palm11-PrRP31 and glucagon-like-peptide-1 agonist liraglutide, substances with anorexigenic and antidiabetic properties, on tau phosphorylation and on the main kinases and phosphatases involved in AD development. Our study was conducted in a neuroblastoma cell line SH-SY5Y and rat primary neuronal cultures under normothermic and hypothermic conditions. Hypothermia induced a significant increase in tau phosphorylation at the pThr212 and pSer396/pSer404 epitopes. The palmitoylated analogs liraglutide and palm11-PrRP31 attenuated tau hyperphosphorylation, suggesting their potential use in the treatment of neurodegenerative diseases.

Neurobiology of Disease, 2002

PLoS ONE, 2014

Tau is a microtubule-associated protein that aggregates in neurodegenerative disorders known as t... more Tau is a microtubule-associated protein that aggregates in neurodegenerative disorders known as tauopathies. Recently, studies have suggested that Tau may be secreted and play a role in neural network signalling. However, once deregulated, secreted Tau may also participate in the spreading of Tau pathology in hierarchical pathways of neurodegeneration. The mechanisms underlying neuron-to-neuron Tau transfer are still unknown; given the known role of extra-cellular vesicles in cell-to-cell communication, we wondered whether these vesicles could carry secreted Tau. We found, among vesicles, that Tau is predominately secreted in ectosomes, which are plasma membrane-originating vesicles, and when it accumulates, the exosomal pathway is activated.

Journal of Biological Chemistry, 2006

Biochemical Society Transactions, 2011

PD (Parkinson's disease) is a neurodegenerative disorder, caused by a selective loss of dopam... more PD (Parkinson's disease) is a neurodegenerative disorder, caused by a selective loss of dopaminergic neurons in the substantia nigra, which affects an increasing number of the elderly population worldwide. One of the major hallmarks of PD is the occurrence of intracellular protein deposits in the dying neurons, termed Lewy bodies, which contain different proteins, including aggregated α-synuclein and its interacting protein synphilin-1. During the last decade, a number of groups developed yeast models that reproduced important features of PD and allowed the deciphering of pathways underlying the cytotoxicity triggered by α-synuclein. Here, we review the recent contributions obtained with yeast models designed to study the presumed pathobiology of synphilin-1. These models pointed towards a crucial role of the sirtuin Sir2 and the chaperonin complex TRiC (TCP-1 ring complex)/CCT (chaperonin containing TCP-1) in handling misfolded and aggregated proteins.

Journal of Biological Chemistry, 2010

Tau-mediated DNA protection in postmitotic neurons. Shown is a scheme illustrating the nuclear Ta... more Tau-mediated DNA protection in postmitotic neurons. Shown is a scheme illustrating the nuclear Tau protection of DNA integrity in heat-stressed neurons.

Additional file 12 : Figure S12. List of oligonucleotides used in mtDNA analysis and in BER assays.

Additional file 9 : Figure S9. PCR-based mtDNA damage analysis. (A) MtDNA damage analysis from 6-... more Additional file 9 : Figure S9. PCR-based mtDNA damage analysis. (A) MtDNA damage analysis from 6-mo Wt (n = 5) and Tg (n = 6) mice CA1 region by long range PCR. (B) MtDNA analysis of 12-mo Wt (n = 5) and Tg (n = 5) mice hippocampi. Data are presented as mean ± SEM. Statistics were performed with unpaired two-tailed Mann-Whitney test (**P

Additional file 8 : Figure S8. Increased mitochondrial Polβ in Tg mice hippocampal neurons. Repre... more Additional file 8 : Figure S8. Increased mitochondrial Polβ in Tg mice hippocampal neurons. Representative immunoelectron microscopy images of CA1 sections from 6-mo Tg and Wt mice hippocampus. The sections were labeled with Polβ antibodies (n = 3 for each mouse category). The scale bars represent 100 nm. Red arrows point Polβ localization

Additional file 7 : Figure S7. Absence of cytoplasmic accumulation of Polβ in 12-mo Tg mice hippo... more Additional file 7 : Figure S7. Absence of cytoplasmic accumulation of Polβ in 12-mo Tg mice hippocampal neurons. Representative images of sagittal CA1 sections from 12-mo Wt and Tg mice hippocampi. The sections were co-labeled with anti-phospho-tau (AT8), and Polβ antibodies (n = 3 for each mouse category). Immunofluorescence signals were analyzed using laser scanning confocal microscopy (z projection). Nuclei were detected with DAPI staining. Representative nuclei are delimitated by white dashed lines. The scale bars represent 20 μm. The intensity of the cellular and nuclear Polβ fluorescence signals was quantified within CA1 cells from 12-mo Wt and Tg hippocampi (nuclei: Wt, n = 84; Tg, n = 66; cellular: Wt, n = 97; Tg, n = 98). Graph shows the mean of nuclear fluorescence per mouse category. Data are presented as mean ± SEM.

Additional file 5 : Figure S5. BER activity is not changed in 12-mo Tg mice. Biochemical analysis... more Additional file 5 : Figure S5. BER activity is not changed in 12-mo Tg mice. Biochemical analysis of BER activity in hippocampal extracts from 12-mo Tg and Wt mice. (A) AP-site incision activity. Recombinant APE1 protein was used as a positive control. (B) Uracil removal activity. Purified recombinant UNG was used as a positive control. (C) 8-oxo-G removal activity Formamidopyrimidine DNA glycosylase (FPG) was used as a positive control. (D) Polβ nucleotide incorporation activity. (E) Quantifications of A-D, data are presented as mean ± SEM.

Additional file 2 : Figure S2. Tau pathology does not affect the expression of the key regulator ... more Additional file 2 : Figure S2. Tau pathology does not affect the expression of the key regulator of mitochondrial biogenesis Pgc1α. WB analysis of extracts from 6-mo Wt and Tg mice CA1 (Wt, n = 6; Tg, n = 5) (A), and from 12-mo Wt and Tg mice hippocampi (Wt, n = 5; Tg, n = 6) (B) for PGC-1α. Actin was used as loading control. Data are presented as mean ± SEM.

Additional file 1 : Figure S1. Tau pathology does not affect mitochondrial mass in CA1 neurons. W... more Additional file 1 : Figure S1. Tau pathology does not affect mitochondrial mass in CA1 neurons. WB analysis of extracts from 6-mo Wt and Tg mice CA1 (Wt, n = 6; Tg, n = 5) (A), and from 12-mo Wt and Tg mice hippocampi (Wt, n = 5; Tg, n = 6) (B) for VDAC1. Actin was used as loading control. Data are presented as mean ± SEM.

Calcium-binding proteins such as calretinin are abundantly expressed in distinctive patterns in t... more Calcium-binding proteins such as calretinin are abundantly expressed in distinctive patterns in the CNS, but their physiological function remains poorly understood. Calretinin is expressed in cerebellar granule cells, which provide the major excitatory input to Purkinje cells through parallel fibers. Calretinin-deficient mice exhibit dramatic alterations in motor coordination and Purkinje cell firing recorded in vivo through unknown mechanisms. In the present study, we used patch-clamp recording techniques in acute slice preparation to investigate the effect of a null mutation of the calretinin gene on the intrinsic electroresponsiveness of cerebellar granule cells at a mature developmental stage. Calretinin-deficient granule cells exhibit faster action potentials and generate repetitive spike discharge showing an enhanced frequency increase with injected currents. These alterations disappear when 0.15 mM of the exogenous fast-calcium buffer BAPTA is infused in the cytosol to restor...

Journal of Alzheimer's Disease, 2019

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases, characteriz... more Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases, characterized by the accumulation of extracellular amyloid plaques and intraneuronal neurofibrillary tangles. These tangles mainly consist of hyperphosphorylated tau protein. As it induces tau hyperphosphorylation in vitro and in vivo, hypothermia is a useful tool for screening potential neuroprotective compounds that ameliorate tau pathology. In this study, we examined the effect of prolactin-releasing peptide (PrRP), its lipidized analog palm11-PrRP31 and glucagon-like-peptide-1 agonist liraglutide, substances with anorexigenic and antidiabetic properties, on tau phosphorylation and on the main kinases and phosphatases involved in AD development. Our study was conducted in a neuroblastoma cell line SH-SY5Y and rat primary neuronal cultures under normothermic and hypothermic conditions. Hypothermia induced a significant increase in tau phosphorylation at the pThr212 and pSer396/pSer404 epitopes. The palmitoylated analogs liraglutide and palm11-PrRP31 attenuated tau hyperphosphorylation, suggesting their potential use in the treatment of neurodegenerative diseases.

Neurobiology of Disease, 2002

PLoS ONE, 2014

Tau is a microtubule-associated protein that aggregates in neurodegenerative disorders known as t... more Tau is a microtubule-associated protein that aggregates in neurodegenerative disorders known as tauopathies. Recently, studies have suggested that Tau may be secreted and play a role in neural network signalling. However, once deregulated, secreted Tau may also participate in the spreading of Tau pathology in hierarchical pathways of neurodegeneration. The mechanisms underlying neuron-to-neuron Tau transfer are still unknown; given the known role of extra-cellular vesicles in cell-to-cell communication, we wondered whether these vesicles could carry secreted Tau. We found, among vesicles, that Tau is predominately secreted in ectosomes, which are plasma membrane-originating vesicles, and when it accumulates, the exosomal pathway is activated.

Journal of Biological Chemistry, 2006

Biochemical Society Transactions, 2011

PD (Parkinson's disease) is a neurodegenerative disorder, caused by a selective loss of dopam... more PD (Parkinson's disease) is a neurodegenerative disorder, caused by a selective loss of dopaminergic neurons in the substantia nigra, which affects an increasing number of the elderly population worldwide. One of the major hallmarks of PD is the occurrence of intracellular protein deposits in the dying neurons, termed Lewy bodies, which contain different proteins, including aggregated α-synuclein and its interacting protein synphilin-1. During the last decade, a number of groups developed yeast models that reproduced important features of PD and allowed the deciphering of pathways underlying the cytotoxicity triggered by α-synuclein. Here, we review the recent contributions obtained with yeast models designed to study the presumed pathobiology of synphilin-1. These models pointed towards a crucial role of the sirtuin Sir2 and the chaperonin complex TRiC (TCP-1 ring complex)/CCT (chaperonin containing TCP-1) in handling misfolded and aggregated proteins.