![]() ![]() Experiments show how RAR signaling may improve axonal regeneration and modulate reactions of glia cells. We review data that imply RAR/RXR and PPAR/RXR pathways in physiological reactions after spinal cord injury. Both receptor families contain ligand-activated transcription factors which form heterodimers with retinoid X receptors (RXR). The retinoid acid receptors ( RAR) and peroxisome proliferator-activated receptors (PPAR) have been implicated in the regulation of inflammatory reactions. RAR/RXR and PPAR/RXR Signaling in Spinal Cord Injury Overall, our studies suggest the clinical potential of ATRA and GSK 3 inhibition for AML and provide a mechanistic framework to explain the promising activity of this combination regimen. These studies have revealed that ATRA's receptor, the retinoic acid receptor ( RAR), is a novel target of GSK 3 phosphorylation and that GSK 3 can impact the expression and transcriptional activity of the RAR. Here we show that the combination of ATRA with glycogen synthase kinase 3 (GSK 3) inhibition significantly enhances ATRA-mediated AML differentiation and growth inhibition. Though many non-APL leukemic cells respond to ATRA, they require significantly higher concentrations of ATRA for effective differentiation. Unfortunately ATRA has not been clinically useful for other subtypes of AML. The use of the differentiation agent, ATRA, in combination with low-dose chemotherapy leads to the long-term survival and presumed cure of 75–85% of patients. The one exception to these poor outcomes is the use of the retinoid, all-trans retinoic acid (ATRA), for a rare subtype of AML (APL). Unfortunately, the standard therapeutic agents used for this disease have high toxicities and poor efficacy. Gupta, K Gulen, F Sun, L Aguilera, R Chakrabarti, A Kiselar, J Agarwal, MK Wald, DNĪcute myeloid leukemia (AML) is the most common form of leukemia in adults. GSK 3 is a regulator of RAR-mediated differentiation ![]()
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