Radicicol potentiates neurotrophin-mediated neurite outgrowth and survival of cultured sensory neurons from chick embryo.

低浓度的自由基可促进鸡胚胎感觉神经元和交感神经元的存活和突起生长。在神经营养素、神经生长因子(NGF)、脑源性神经营养因子(BDNF)和神经营养素-3(NT-3)饱和的情况下，培养的背根节(DRG)神经元对抗肿瘤药物顺铂、长春新碱和紫杉醇极为敏感。这些抗癌药物的神经毒性作用可通过向培养物中添加20 NM的自由基完全阻止。最近的研究表明，自由基和格尔达霉素的主要细胞内靶点是热休克蛋白90(HSP90)伴侣，干扰其功能。在有无神经营养因子的情况下，低剂量(约2 NM)格尔达霉素对DRG神经元也有神经营养作用，但较高剂量(&GT；5 NM)对神经元有严重的细胞毒作用。低剂量的格尔达那霉素也被发现对抗癌药物如自由基具有神经保护作用。然而，在没有神经营养素的情况下，较高剂量的自由基(500 NM)仍可诱导神经元突起并阻止其凋亡。用最佳剂量的格尔达那霉素和自由基一起治疗神经元是细胞毒性而不是神经营养。这两种抗生素可能有共同的靶点，对培养的神经元具有营养和毒性作用。然而，两种抗生素之间的细胞作用差异并不能很好地解释。推测这种新的活性可能是通过抑制热休克蛋白90的功能来实现的，尽管我不能排除有限剂量的抗生素与热休克蛋白90以外的特异性靶分子(S)相互作用从而抑制细胞凋亡的可能性。这些结果表明，自由基对神经退行性疾病，特别是对抗癌药物所致感觉神经病具有治疗潜力。

The low concentration of radicicol enhanced the survival and neurite outgrowth of the embryonic sensory and sympathetic neurons from chick embryos. The cultured dorsal root ganglion (DRG) neurons were extremely susceptible to the antineoplastic drugs, cisplatin, vincristine and taxol even in the presence of saturating levels of the neurotrophins, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). The neurotoxic effects of these anti-cancer drugs were completely prevented by the addition of radicicol (20 nM) to the cultures. Recent studies showed that the major intracellular target of radicicol and geldanamycin is the heat shock protein 90 (HSP90) chaperone, interfering with its function. Geldanamycin at low doses (about 2 nM) appeared to also be neurotrophic on DRG neurons in the presence or absence of neurotrophins, but higher doses of geldanamycin (>5 nM) had severe cytotoxic effects on neurons. Geldanamycin at low doses was also found to be neuroprotective against anti-cancer drugs as radicicol. Higher doses of radicicol (500 nM), however, still induced neurites and prevented apoptosis of the isolated DRG neurons in the absence of neurotrophins. Treatment of neurons with optimal doses of geldanamycin and radicicol together was cytotoxic instead of neurotrophic. These two antibiotics may share a common target and provide trophic and toxic effect to the cultured neurons. While different cellular effects between two antibiotics were not well explicable. It is presumed that the novel activity might be mediated via suppression of HSP90 function, although I can not rule out the possibility that limited doses of these antibiotics interact with specicfic target molecule (s) other than HSP90 and suppress apoptosis. These results indicated that radicicol has therapeutic potential for neurodegenerative diseases, especially for anti-cancer drug-induced sensory neuropathy.