scholarly journals Miro1 Impairment in a Parkinson’s At-Risk Cohort

2021 ◽  
Vol 14 ◽  
Author(s):  
David Nguyen ◽  
Vinita Bharat ◽  
Devon M. Conradson ◽  
Pawan Nandakishore ◽  
Xinnan Wang

There is a lack of reliable molecular markers for Parkinson’s disease (PD) patients and at-risk individuals. The detection of the pre-symptomatic population of PD will empower more effective clinical intervention to delay or prevent disease onset. We have previously found that the mitochondrial protein Miro1 is resistant to mitochondrial depolarization-induced degradation in fibroblasts from a large number of PD patients and several at-risk individuals. Therefore, Miro1 has the potential to molecularly label PD populations. In order to determine whether Miro1 could serve as a molecular marker for the risk of PD, here we examine the Miro1 response to mitochondrial depolarization by biochemical approaches in induced pluripotent stem cells from a cohort of at-risk individuals. Our results show that the Miro1 phenotype is significantly associated with PD risk. We propose that Miro1 is a promising molecular marker for detecting both PD and at-risk populations. Tracking this Miro1 marker could aid in diagnosis and Miro1-based drug discoveries.

2016 ◽  
Vol 215 (2) ◽  
pp. 187-202 ◽  
Author(s):  
Lili Zhu ◽  
Aurora Gomez-Duran ◽  
Gabriele Saretzki ◽  
Shibo Jin ◽  
Katarzyna Tilgner ◽  
...  

Human induced pluripotent stem cell (hiPSC) utility is limited by variations in the ability of these cells to undergo lineage-specific differentiation. We have undertaken a transcriptional comparison of human embryonic stem cell (hESC) lines and hiPSC lines and have shown that hiPSCs are inferior in their ability to undergo neuroectodermal differentiation. Among the differentially expressed candidates between hESCs and hiPSCs, we identified a mitochondrial protein, CHCHD2, whose expression seems to correlate with neuroectodermal differentiation potential of pluripotent stem cells. We provide evidence that hiPSC variability with respect to CHCHD2 expression and differentiation potential is caused by clonal variation during the reprogramming process and that CHCHD2 primes neuroectodermal differentiation of hESCs and hiPSCs by binding and sequestering SMAD4 to the mitochondria, resulting in suppression of the activity of the TGFβ signaling pathway. Using CHCHD2 as a marker for assessing and comparing the hiPSC clonal and/or line differentiation potential provides a tool for large scale differentiation and hiPSC banking studies.


2010 ◽  
Vol 34 (8) ◽  
pp. S36-S36
Author(s):  
Ping Duan ◽  
Xuelin Ren ◽  
Wenhai Yan ◽  
Xuefei Han ◽  
Xu Yan ◽  
...  

Acta Naturae ◽  
2009 ◽  
Vol 1 (2) ◽  
pp. 91-92 ◽  
Author(s):  
M V Shutova ◽  
A N Bogomazova ◽  
M A Lagarkova ◽  
S L Kiselev

2014 ◽  
Author(s):  
Talluri Thirumala Rao ◽  
Dharmendra Kumar ◽  
Silke Glage ◽  
Wiebke Garrels ◽  
Katharina Debowski ◽  
...  

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