Unconventional neurotrophic factors CDNF and MANF: Structure, physiological functions and therapeutic potential

2017 ◽  
Vol 97 ◽  
pp. 90-102 ◽  
Author(s):  
Maria Lindahl ◽  
Mart Saarma ◽  
Päivi Lindholm
2012 ◽  
Vol 140 (6) ◽  
pp. 275-279 ◽  
Author(s):  
Takafumi Hara ◽  
Akira Hirasawa ◽  
Atsuhiko Ichimura ◽  
Ikuo Kimura ◽  
Gozoh Tsujimoto

Author(s):  
Ava Nasrolahi ◽  
Fatemeh Javaherforooshzadeh ◽  
Mohsen Jafarzadeh-Gharehziaaddin ◽  
Javad Mahmoudi ◽  
Khadijeh Dizaji Asl ◽  
...  

2020 ◽  
Vol 318 (4) ◽  
pp. H801-H815
Author(s):  
Jessica M. Miller ◽  
Nikhil M. Mardhekar ◽  
Danielle Pretorius ◽  
Prasanna Krishnamurthy ◽  
Namakkal Soorappan Rajasekaran ◽  
...  

DNA damage accrued in induced pluripotent stem cell (iPSC)-derived cardiomyocytes during in vitro culture practices lessens their therapeutic potential. We determined whether DNA-damage-free iPSCs (DdF-iPSCs) can be selected using stabilization of p53, a transcription factor that promotes apoptosis in DNA-damaged cells, and differentiated them into functionally competent DdF cardiomyocytes (DdF-CMs). p53 was activated using Nutlin-3a in iPSCs to selectively kill the DNA-damaged cells, and the stable DdF cells were cultured further and differentiated into CMs. Both DdF-iPSCs and DdF-CMs were then characterized. We observed a significant decrease in the expression of reactive oxygen species and DNA damage in DdF-iPSCs compared with control (Ctrl) iPSCs. Next-generation RNA sequencing and Ingenuity Pathway Analysis revealed improved molecular, cellular, and physiological functions in DdF-iPSCs. The differentiated DdF-CMs had a compact beating frequency between 40 and 60 beats/min accompanied by increased cell surface area. Additionally, DdF-CMs were able to retain the improved molecular, cellular, and physiological functions after differentiation from iPSCs, and, interestingly, cardiac development network was prominent compared with Ctrl-CMs. Enhanced expression of various ion channel transcripts in DdF-CMs implies DdF-CMs are of ventricular CMs and mature compared with their counterparts. Our results indicated that DdF-iPSCs could be selected through p53 stabilization using a small-molecule inhibitor and differentiated into ventricular DdF-CMs with fine-tuned molecular signatures. These iPSC-derived DdF-CMs show immense clinical potential in repairing injured myocardium. NEW & NOTEWORTHY Culture-stress-induced DNA damage in stem cells lessens their performance. A robust small-molecule-based approach, by stabilizing/activating p53, to select functionally competent DNA-damage-free cells from a heterogeneous population of cells is demonstrated. This protocol can be adopted by clinics to select DNA-damage-free cells before transplanting them to the host myocardium. The intact DNA-damage-free cells exhibited with fine-tuned molecular signatures and improved cellular functions. DNA-damage-free cardiomyocytes compared with control expressed superior cardiomyocyte functional properties, including, but not limited to, enhanced ion channel signatures. These DNA-intact cells would better engraft, survive, and, importantly, improve the cardiac function of the injured myocardium.


2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Tatsuhito Himeno ◽  
Hideki Kamiya ◽  
Keiko Naruse ◽  
Zhao Cheng ◽  
Sachiko Ito ◽  
...  

Background. Although pathological involvements of diabetic polyneuropathy (DPN) have been reported, no dependable treatment of DPN has been achieved. Recent studies have shown that mesenchymal stem cells (MSCs) ameliorate DPN. Here we demonstrate a differentiation of induced pluripotent stem cells (iPSCs) into MSC-like cells and investigate the therapeutic potential of the MSC-like cell transplantation on DPN.Research Design and Methods. For induction into MSC-like cells, GFP-expressing iPSCs were cultured with retinoic acid, followed by adherent culture for 4 months. The MSC-like cells, characterized with flow cytometry and RT-PCR analyses, were transplanted into muscles of streptozotocin-diabetic mice. Three weeks after the transplantation, neurophysiological functions were evaluated.Results. The MSC-like cells expressed MSC markers and angiogenic/neurotrophic factors. The transplanted cells resided in hindlimb muscles and peripheral nerves, and some transplanted cells expressed S100βin the nerves. Impairments of current perception thresholds, nerve conduction velocities, and plantar skin blood flow in the diabetic mice were ameliorated in limbs with the transplanted cells. The capillary number-to-muscle fiber ratios were increased in transplanted hindlimbs of diabetic mice.Conclusions. These results suggest that MSC-like cell transplantation might have therapeutic effects on DPN through secreting angiogenic/neurotrophic factors and differentiation to Schwann cell-like cells.


BioDrugs ◽  
2005 ◽  
Vol 19 (2) ◽  
pp. 97-127 ◽  
Author(s):  
Yossef S Levy ◽  
Yossi Gilgun-Sherki ◽  
Eldad Melamed ◽  
Daniel Offen

2021 ◽  
Author(s):  
Monireh Khordadmehr ◽  
Reyhaneh Matin ◽  
Behzad Baradaran ◽  
Amir Baghbanzadeh ◽  
Farinaz Jigari-Asl ◽  
...  

MicroRNAs (miRNAs) are known as a group of short noncoding ribonucleic acids (ncRNAs). Mainly, they can manage gene expression at the posttranscriptional level in the essential biological and physiological functions. Significantly, more than 50% of the discovered miRNAs genes are placed in cancer‐related genomic regions, which can act as oncomiR or oncosuppressor. In this regard, growing evidence recently demonstrated the deregulation of miR-4800 in human cancers and non-cancerous diseases. However, little information is available on the biological roles of miR-4800 in cancer initiation, development, and progression. Here, we reviewed the targeting sites and biogenesis functions of the miR‐4800 family in physiological and pathological processes like human cancers, particularly with a particular focusing on the validated specific targets.


2020 ◽  
Vol 382 (1) ◽  
pp. 173-183 ◽  
Author(s):  
Pia Runeberg-Roos ◽  
Richard D Penn

Abstract The last decade has been a frustrating time for investigators who had envisioned major advances in the treatment of Parkinson’s disease using neurotrophic factors. The first trials of glial cell line–derived neurotrophic factor for treating Parkinson’s disease were very promising. Later blinded control trials were disappointing, not reaching the predetermined outcomes for improvement in motor function. Consideration of the problems in the studies as well as the biology of the neurotrophins used can potentially lead to more effective therapies. Parkinson’s disease presents a multitude of opportunities for the cell biologist wanting to understand its pathology and to find possible new avenues for treatment.


2000 ◽  
Vol 20 (10) ◽  
pp. 1393-1408 ◽  
Author(s):  
Koji Abe

Development of neuronal and glial cells and their maintenance are under control of neurotrophic factors (NTFs). An exogenous administration of NTFs protects extremely sensitive brain tissue from ischemic damage. On the other hand, it is now known that neural stem cells are present in normal adult brain, and have a potential to compensate and recover neural functions that were lost due to ischemic stroke. These stem cells are also under control of NTFs to differentiate into a certain species of neural cells. Thus, the purpose of this review is to summarize the present understanding of the role of NTFs in normal and ischemic brain and the therapeutic potential of NTF protein itself or gene therapy, and then to summarize the role of NTFs in stem cell differentiation and a possible therapeutic potential with the neural stem cells against ischemic brain injury.


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