scholarly journals Age-related Purkinje cell death is steroid dependent: RORα haplo-insufficiency impairs plasma and cerebellar steroids and Purkinje cell survival

AGE ◽  
2011 ◽  
Vol 33 (4) ◽  
pp. 565-578 ◽  
Author(s):  
Sonja Janmaat ◽  
Yvette Akwa ◽  
Mohamed Doulazmi ◽  
Joëlle Bakouche ◽  
Vanessa Gautheron ◽  
...  
2010 ◽  
Vol 10 (2) ◽  
pp. 281-290 ◽  
Author(s):  
Mariaelena Repici ◽  
Rosine Wehrlé ◽  
Xanthi Antoniou ◽  
Tiziana Borsello ◽  
Isabelle Dusart

2021 ◽  
Author(s):  
George garinis ◽  
Katerina Gkirtzimanaki ◽  
Edisona Tsakani ◽  
Ermioni Arvanitaki ◽  
Electra Nenedaki ◽  
...  

Abstract Neurodegenerative disorders are a growing challenge for the elderly yet their etiology remains elusive. Here, we show that persistent DNA damage in tissue-resident macrophages carrying an ERCC1-XPF DNA repair defect leads to cerebellar ataxia in mice. We find that cytoplasmic chromatin fragments accumulate in the brain microglia of progeroid and naturally aged mice stimulating a type-I Interferon (IFN-I) response and are then packaged in extracellular vesicles (EVs) leading to Purkinje cell death and neurodegeneration in Er1CX/− animals. To reduce neuroinflammation, we developed an EV-based strategy to deliver recombinant DNase I specifically in inflamed Er1CX/− microglia in vivo. Our approach rapidly removes dsDNAs from the cytoplasm of microglial cells and in secreted EVs; it alleviates the IFN-I response, decreases Purkinje cell death and delays the onset of neuronal decline in Er1CX/− animals. Thus, brain microglia causally contribute to neurodegeneration allowing for the development of promising therapeutic strategies against age-related neuroinflammation.


2000 ◽  
Vol 12 (8) ◽  
pp. 2935-2949 ◽  
Author(s):  
Abdel M. Ghoumari ◽  
Rosine Wehrlé ◽  
Ora Bernard ◽  
Constantino Sotelo ◽  
Isabelle Dusart

1993 ◽  
Vol 52 (3) ◽  
pp. 286
Author(s):  
H. B. Clark ◽  
H. T. Orr ◽  
R. Ehlenfeldt ◽  
W. S. Yunis ◽  
R. M. Feddersen

2015 ◽  
Vol 7 (276) ◽  
pp. 276ra26-276ra26 ◽  
Author(s):  
Charles H. Vite ◽  
Jessica H. Bagel ◽  
Gary P. Swain ◽  
Maria Prociuk ◽  
Tracey U. Sikora ◽  
...  

2017 ◽  
Vol 58 (3) ◽  
pp. 512-518 ◽  
Author(s):  
Chang Xie ◽  
Xue-Min Gong ◽  
Jie Luo ◽  
Bo-Liang Li ◽  
Bao-Liang Song

2002 ◽  
Vol 22 (9) ◽  
pp. 3531-3542 ◽  
Author(s):  
Abdel M. Ghoumari ◽  
Rosine Wehrlé ◽  
Chris I. De Zeeuw ◽  
Constantino Sotelo ◽  
Isabelle Dusart

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