Radiation is an important modality in cancer treatment, and eighty percent of cancer patients need radiotherapy at some point during their clinical management. However, radiation-induced damage to normal tissues restr...Radiation is an important modality in cancer treatment, and eighty percent of cancer patients need radiotherapy at some point during their clinical management. However, radiation-induced damage to normal tissues restricts the therapeutic doses of radiation that can be delivered to tumours and thereby limits the effectiveness of the treatment. The use of radioprotectors represents an obvious strategy to obtain better tumour control using a higher dose in radiotherapy. However, most of the synthetic radioprotective compounds studied have shown inadequate clinical efficacy owing to their inherent toxicity and high cost. Hence, the development of radioprotective agents with lower toxicity and an extended window of protection has attracted a great deal of attention, and the identification of alternative agents that are less toxic and highly effective is an absolute necessity. Recent studies have shown that alpha-2-macroglobulin（α2M） possesses radioprotective effects. α2M is a tetrameric, disulfide-rich plasma glycoprotein that functions as a nonselective inhibitor of different types of non-specific proteases and as a carrier of cytokines, growth factors, and hormones. α2M induces protein factors whose interplay underlies radioprotection, which supports the idea that α2M is the central effector of natural radioprotection in the rat. Pretreatment with α2M has also induced a significant reduction of irradiation-induced DNA damage and the complete restoration of liver and body weight. Mihailovi？ et al. concluded that the radioprotection provided by α2M was in part mediated through cytoprotection of new blood cells produced in the bone marrow; these authors also indicated that an important aspect of the radioprotective effect of amifostine was the result of the induction of the endogenous cytoprotective capability of α2M. The radioprotective effects of α2M are possibly due to antioxidant, antifibrosis, and anti-inflammatory functions, as well as the maintenance of homeostasis, and enhancement of the DNA repair and cell recovery processes. This review is the first to summarise the observations and elucidate the possible mechanisms responsible for the beneficial effects of α2M. The lacunae in the existing knowledge and directions for future research are also addressed.展开更多
Recent studies suggest that the activation of the Wnt signaling pathway improves memory function in rats.This study investigated the effects of Wnt-5a on amyloid β （Aβ）-induced cognitive impairment.Aβ25-35 was in...Recent studies suggest that the activation of the Wnt signaling pathway improves memory function in rats.This study investigated the effects of Wnt-5a on amyloid β （Aβ）-induced cognitive impairment.Aβ25-35 was injected into the rat right lateral ventricle to induce Alzheimer＇s disease-associated pathology,and Wnt-5a was injected as a potential therapeutic treatment.Immunofluorescence staining showed that compared with normal rats,Aβ25-35 significantly decreased postsynaptic density-95 protein expression in the rat hippocampal CA1 region,but Wnt-5a pretreatment blocked this decrease.This study shows that Wnt-5a can reduce Aβ-induced cognitive impairment,and that it has the potential to be a new therapeutic strategy for the treatment of Alzheimer＇s disease.展开更多
基金supported by grant of the Science and Technology Planning Project of Guangdong Province (2010B060900052 and 2009B030801186)the Fundamental Research Funds for the Central Universities (the Young Teacher Training Project of Sun Yat-sen University 09ykpy12)the Medical Scientific Research Project of Zhuhai City (2012003)
文摘Radiation is an important modality in cancer treatment, and eighty percent of cancer patients need radiotherapy at some point during their clinical management. However, radiation-induced damage to normal tissues restricts the therapeutic doses of radiation that can be delivered to tumours and thereby limits the effectiveness of the treatment. The use of radioprotectors represents an obvious strategy to obtain better tumour control using a higher dose in radiotherapy. However, most of the synthetic radioprotective compounds studied have shown inadequate clinical efficacy owing to their inherent toxicity and high cost. Hence, the development of radioprotective agents with lower toxicity and an extended window of protection has attracted a great deal of attention, and the identification of alternative agents that are less toxic and highly effective is an absolute necessity. Recent studies have shown that alpha-2-macroglobulin（α2M） possesses radioprotective effects. α2M is a tetrameric, disulfide-rich plasma glycoprotein that functions as a nonselective inhibitor of different types of non-specific proteases and as a carrier of cytokines, growth factors, and hormones. α2M induces protein factors whose interplay underlies radioprotection, which supports the idea that α2M is the central effector of natural radioprotection in the rat. Pretreatment with α2M has also induced a significant reduction of irradiation-induced DNA damage and the complete restoration of liver and body weight. Mihailovi？ et al. concluded that the radioprotection provided by α2M was in part mediated through cytoprotection of new blood cells produced in the bone marrow; these authors also indicated that an important aspect of the radioprotective effect of amifostine was the result of the induction of the endogenous cytoprotective capability of α2M. The radioprotective effects of α2M are possibly due to antioxidant, antifibrosis, and anti-inflammatory functions, as well as the maintenance of homeostasis, and enhancement of the DNA repair and cell recovery processes. This review is the first to summarise the observations and elucidate the possible mechanisms responsible for the beneficial effects of α2M. The lacunae in the existing knowledge and directions for future research are also addressed.
文摘Recent studies suggest that the activation of the Wnt signaling pathway improves memory function in rats.This study investigated the effects of Wnt-5a on amyloid β （Aβ）-induced cognitive impairment.Aβ25-35 was injected into the rat right lateral ventricle to induce Alzheimer＇s disease-associated pathology,and Wnt-5a was injected as a potential therapeutic treatment.Immunofluorescence staining showed that compared with normal rats,Aβ25-35 significantly decreased postsynaptic density-95 protein expression in the rat hippocampal CA1 region,but Wnt-5a pretreatment blocked this decrease.This study shows that Wnt-5a can reduce Aβ-induced cognitive impairment,and that it has the potential to be a new therapeutic strategy for the treatment of Alzheimer＇s disease.
