Targeting survivin has the ability to inhibit apoptosis and regulate mitosis for the protection of neuronal cells, and it offers several advantages for neuronal repair and protection. We found that the BIR motif mutant of survivin (SurR9-C84A) can bind to microtubules and regulate their stability, induce cell division, increase proliferation and activate the expression of cell cycle and neuronal markers in differentiated SK-N-SH and HCN-2 neurons. We further showed the protective effects of SurR9-C84A against post differentiation retinoic acid induced neurotoxicity. These abilities of SurR9-C84A offer a great potential for future neuronal repair therapy.
"Likewise, we have identified that the mutant form of survivin, SurR9-C84A (baculovirus inhibitor of apoptosis repeat motif) has solid neuroprotective activity when tested in SK-N-SH cells subjected to oxidative stress induced by hydrogen peroxide.165 Following this, we also identified the potential of SurR9-C84A in stimulating neuronal proliferation, survival, and expression of neuronal markers when tested in SK-N-SH and HCN-2 cell lines.166 Further to this, we also noted the neuroprotective and mitogenic effects of BARF1 epitopes of Epstein-Barr virus.167 "
[Show abstract][Hide abstract] ABSTRACT: We are now in an aging population, so neurological disorders, particularly the neurodegenerative diseases, are becoming more prevalent in society. As per the epidemiological studies, Europe alone suffers 35% of the burden, indicating an alarming rate of disease progression. Further, treatment for these disorders is a challenging area due to the presence of the tightly regulated blood-brain barrier and its unique ability to protect the brain from xenobiotics. Conventional therapeutics, although effective, remain critically below levels of optimum therapeutic efficacy. Hence, methods to overcome the blood-brain barrier are currently a focus of research. Nanotechnological applications are gaining paramount importance in addressing this question, and yielding some promising results. This review addresses the pathophysiology of the more common neurological disorders and novel drug candidates, along with targeted nanoparticle applications for brain delivery.
International Journal of Nanomedicine 07/2012; 7:3259-78. DOI:10.2147/IJN.S30919 · 4.38 Impact Factor
"In studying the neuroproliferative and protective effects of SurR9-84A, an IAP repeat mutant of survivin, we found a strong neuroprotective effect against the release of soluble inflammatory mediators from activated T-cells and hydrogen peroxide-mediated oxidative stress. These effects were due to the role of SurR9-84A in altering mitochondrial permeability, balancing calcium homeostasis and inhibiting apoptosis (Baratchi et al., 2010). "
[Show abstract][Hide abstract] ABSTRACT: Apoptosis is an important contributing factor during neuronal death in a variety of neurodegenerative disorders, including multiple sclerosis, Parkinson's disease and sciatic nerve injury. Whereas several clinical and preclinical studies have focused on the neuroprotective effects of caspase inhibitors, their clinical benefits are still unclear. Here, we discuss novel alternative strategies to protect neuronal cells from apoptotic death using members of the inhibitors of apoptosis (IAP) family. We specifically review the different roles of survivin, which is an important member of the IAP family that serves a dual role in the inhibition of apoptosis as well as a vital role in mitosis and cell division. Due to the various roles of survivin during cell division and apoptosis, targeting this protein illustrates a new therapeutic window for the treatment of neurodegenerative diseases.
Critical Reviews in Biochemistry and Molecular Biology 10/2010; 45(6):535-54. DOI:10.3109/10409238.2010.516740 · 7.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dramatic progress in GaN electronics has led to increased interest
in bipolar transistors. Although there have been reports of GaN bipolars
from several groups, the development of the GaN bipolar transistor is
still in its fundamental stages. In the case of GaN, the usual
correlation between common base, Gummel, and common emitter
characteristics does not exist due to significant collector-emitter
leakage, leaving only the common emitter characteristic as a reliable
measure of DC device performance. We identify the source of this leakage
as threading dislocations and clarify the effect of this leakage on the
transistor DC characteristics. Furthermore, we conclude from various
growth structures and methods of device fabrication that the electron
lifetime in the neutral base is currently the limiting factor in GaN NPN
transistor performance. Typical GaN material has high threading
dislocation densities, 10<sup>7</sup>-10<sup>9</sup> cm<sup>-2</sup>,
due to lattice mismatch with the substrate, typically sapphire or SiC.
To study the effects of threading dislocations on GaN bipolar
transistors, we have fabricated devices on material grown using the
lateral epitaxial overgrowth technique, LEO. To the authors' knowledge,
this is the first demonstration of GaN bipolar transistors grown on
nondislocated material. The LEO substrate allows us to compare devices
grown on material with a negligible dislocation density with those grown
on a standard template
Device Research Conference, 2000. Conference Digest. 58th DRC; 02/2000
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