scholarly journals Generation of induced pluripotent stem cells from a young-onset Parkinson's disease patient carrying the compound heterozygous PLA2G6 p.D331Y/p.M358IfsX mutations

2019 ◽  
Vol 40 ◽  
pp. 101552
Author(s):  
Ching-Chi Chiu ◽  
Hung-Li Wang ◽  
Yi-Hsin Weng ◽  
Rou-Shayn Chen ◽  
Chiung-Mei Chen ◽  
...  
Cell ◽  
2009 ◽  
Vol 137 (7) ◽  
pp. 1356 ◽  
Author(s):  
Frank Soldner ◽  
Dirk Hockemeyer ◽  
Caroline Beard ◽  
Qing Gao ◽  
George W. Bell ◽  
...  

Cell ◽  
2009 ◽  
Vol 136 (5) ◽  
pp. 964-977 ◽  
Author(s):  
Frank Soldner ◽  
Dirk Hockemeyer ◽  
Caroline Beard ◽  
Qing Gao ◽  
George W. Bell ◽  
...  

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Vasiliki Panagiotakopoulou ◽  
Dina Ivanyuk ◽  
Silvia De Cicco ◽  
Wadood Haq ◽  
Aleksandra Arsić ◽  
...  

Abstract Parkinson’s disease-associated kinase LRRK2 has been linked to IFN type II (IFN-γ) response in infections and to dopaminergic neuronal loss. However, whether and how LRRK2 synergizes with IFN-γ remains unclear. In this study, we employed dopaminergic neurons and microglia differentiated from patient-derived induced pluripotent stem cells carrying LRRK2 G2019S, the most common Parkinson’s disease-associated mutation. We show that IFN-γ enhances the LRRK2 G2019S-dependent negative regulation of AKT phosphorylation and NFAT activation, thereby increasing neuronal vulnerability to immune challenge. Mechanistically, LRRK2 G2019S suppresses NFAT translocation via calcium signaling and possibly through microtubule reorganization. In microglia, LRRK2 modulates cytokine production and the glycolytic switch in response to IFN-γ in an NFAT-independent manner. Activated LRRK2 G2019S microglia cause neurite shortening, indicating that LRRK2-driven immunological changes can be neurotoxic. We propose that synergistic LRRK2/IFN-γ activation serves as a potential link between inflammation and neurodegeneration in Parkinson’s disease.


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Xinchao Hu ◽  
Chengyuan Mao ◽  
Liyuan Fan ◽  
Haiyang Luo ◽  
Zhengwei Hu ◽  
...  

Parkinson’s disease (PD) is the second most common neurodegenerative disease. The molecular mechanisms of PD at the cellular level involve oxidative stress, mitochondrial dysfunction, autophagy, axonal transport, and neuroinflammation. Induced pluripotent stem cells (iPSCs) with patient-specific genetic background are capable of directed differentiation into dopaminergic neurons. Cell models based on iPSCs are powerful tools for studying the molecular mechanisms of PD. The iPSCs used for PD studies were mainly from patients carrying mutations in synuclein alpha (SNCA), leucine-rich repeat kinase 2 (LRRK2), PTEN-induced putative kinase 1 (PINK1), parkin RBR E3 ubiquitin protein ligase (PARK2), cytoplasmic protein sorting 35 (VPS35), and variants in glucosidase beta acid (GBA). In this review, we summarized the advances in molecular mechanisms of Parkinson’s disease using iPSC models.


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