VA Boston Healthcare System, Boston, MA 02130, USA; Neurology and Alzheimer's Disease Center, Boston University School of Medicine, Boston, MA 02118, USA; Physiology and Neurophysiology, Medical Faculty, Eskisehir Osmangazi University, Eskisehir 26480, Turkey.
VA Boston Healthcare System, Boston, MA 02130, USA; Neurology and Alzheimer's Disease Center, Boston University School of Medicine, Boston, MA 02118, USA.
Neurosci Lett. 2014 Apr 30;566:286-91. doi: 10.1016/j.neulet.2014.02.058. Epub 2014 Mar 15.
Amyotrophic lateral sclerosis (ALS) is an enigmatic neurodegenerative disorder without any effective treatment characterized by loss of motor neurons (MNs) that results in rapidly progressive motor weakness and early death due to respiratory failure. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family known to play a prominent role in the differentiation and survival of MNs. The flavonoid 7,8-dihydroxyflavone (7,8-DHF) is a potent and selective small molecule tyrosine kinase receptor B (TrkB) agonist that mimics the effects of BDNF. In the present study, we evaluated the neuroprotective effects of 7,8-DHF in a transgenic ALS mouse model (SOD1(G93A)). We found that chronic administration of 7,8-DHF significantly improved motor deficits, and preserved spinal MNs count and dendritic spines in SOD1(G93A) mice. These data suggest that 7,8-DHF should be considered as a potential therapy for ALS and the other motor neuron diseases.
肌萎缩侧索硬化症（ALS）是一种神秘的神经退行性疾病，没有任何有效的治疗方法，其特征是运动神经元（MNs）的丧失，导致运动无力迅速进展，并因呼吸衰竭而导致早期死亡。脑源性神经营养因子（BDNF）是神经营养因子家族的一员，已知其在 MNs 的分化和存活中起重要作用。类黄酮 7,8-二羟基黄酮（7,8-DHF）是一种有效的选择性小分子酪氨酸激酶受体 B（TrkB）激动剂，可模拟 BDNF 的作用。在本研究中，我们评估了 7,8-DHF 在转基因 ALS 小鼠模型（SOD1（G93A））中的神经保护作用。我们发现，7,8-DHF 的慢性给药可显著改善运动缺陷，并可维持 SOD1（G93A）小鼠脊髓 MNs 的数量和树突棘。这些数据表明，7,8-DHF 可被视为 ALS 和其他运动神经元疾病的一种潜在治疗方法。
