An older study on AS101, not AS1011:
Tellurium Compound AS101 Induces PC12 Differentiation and Rescues the Neurons from Apoptotic Death
D MAKAROVSKYa, Y KALECHMANa, T SONINOa, I FREIDKINa, S TEITZa, M ALBECKa, M WEILb, R GEFFEN-ARICHAa, G YADIDa AND B SREDNIa
aC.A.I.R. Institute, Faculty of Life Science, Bar Ilan University, Ramat Gan, 59200 Israel
bDepartment of Cell Research and Immunology, Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Israel
Address for correspondence: Dr. B. Sredni, C.A.I.R. Institute, Faculty of Life Science, Bar Ilan University, Ramat Gan, 59200 Israel. Voice: +972-3 531-8250; fax: +972-3 635-6041.
srednib@mail.biu.ac.il
Ann. N.Y. Acad. Sci. 1010: 659-666 (2003).
Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra (SN). Studies show that anti-apoptotic and neurotrophic agents are suitable candidates to prevent delayed cell death and/or restore neural function.
Here we present the nontoxic immunomodulating compound AS101, which has the ability to induce neurite outgrowth and neural differentiation in PC12 cells. The present study shows that components of the ras signaling pathway are crucial for AS101-induced PC12 differentiation.
These include p21ras and its downstream effectors, c-raf-1 and MEK, as well as PI3K. Moreover, these components mediate AS101-induced upregulation of p21waf, which is obligatory for AS101-induced PC12 differentiation. Furthermore, nitric oxide plays a significant role in these AS101 activities.
Finally, we show that AS101 prevents apoptosis of NGF-differentiated PC12 cells after NGF withdrawal
Taken together, these results suggest that AS101 induces PC12 cell differentiation and survival by activating the ras-ERK1/2 and ras-PI3K signal transduction pathways, as well as inducing NO production.
Our findings may be important in understanding the regulation of survival/apoptosis of neurons deprived of neurotropic support. Futhermore the data propose that AS101 may have clinical potential in the treatment of neurodegenerative disorders like Parkinson's disease.
http://www.annalsonline.org/cgi/cont...act/1010/1/659