title: Patents for Toll-like receptor ligands as radiation countermeasures for acute radiation syndrome.
abstract: Acute radiation exposure induces apoptosis of tissues in the hematopoietic, digestive, cutaneous, cardiovascular and nervous systems; extensive apoptosis of these tissues ultimately leads to acute radiation syndrome. A novel strategy for developing radiation countermeasures has been to imitate the genetic mechanisms acquired by radiation-resistant tumors. Two mechanisms that underlie this ability of tumor cells are the p53 and NF-κB pathways. The loss of p53 function results in the inactivation of pro-apoptotic control mechanisms, while constitutive activation of NF-κB results in the up-regulation of anti-apoptotic genes. Various Toll-like receptor ligands are capable of up regulating the NF-κB pathway, which increases radio-resistance and reduces radiation-induced apoptosis in various tissues. Several Toll-like receptor ligands have been patented and are currently under development as radiation countermeasures for acute radiation syndrome. Ongoing studies suggest that a few of these attractive agents are progressing well along the US FDA approval pathway to become radiation countermeasures.
authors.affiliation: a 1 Armed Forces Radiobiology Research Institute , Bethesda, MD, USA +1 301 295 2347 ; +1 301 295 6503 ; vijay.singh@usuhs.edu.|b 2 Department of Radiation Biology, F. Edward Hébert School of Medicine "America's Medical School", Uniformed Services University of the Health Sciences , Bethesda, MD, USA.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Singh
authors.affiliation: c 3 Department of Anatomy, Physiology and Genetics, F. Edward Hébert School of Medicine "America's Medical School", Uniformed Services University of the Health Sciences , Bethesda, MD, USA.
authors.forename: Harvey B
authors.initials: HB
authors.lastname: Pollard
mesh_terms: D054508:Acute Radiation Syndrome / Q000188:drug therapy*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008024:Ligands; D016328:NF-kappa B / Q000378:metabolism; D010330:Patents as Topic; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051193:Toll-Like Receptors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D008024:Ligands; D016328:NF-kappa B; D011837:Radiation-Protective Agents; D051193:Toll-Like Receptors; D016159:Tumor Suppressor Protein p53
keywords: NF-κB; Toll-like receptor ligands; acute radiation syndrome; radiation