Department of Physiology, Medical Faculty, Eskisehir Osmangazi University, Eskisehir, 26040, Türkiye.
Curr Pharm Des. 2023;29(4):246-250. doi: 10.2174/1381612829666230127142414.
Neurodegenerative diseases are chronic and progressive disease groups characterized by the decline of neural transmission because of the loss of structure and function of neurons. Although there is currently no effective treatment for neurodegenerative diseases, new treatment strategies need to be developed urgently. Among neurotrophins, BDNF has been extensively investigated, and it has emerged as an important regulator of synaptic plasticity, neuronal survival, and differentiation. Changes in BDNF levels and signaling pathways have been identified in several neurodegenerative diseases. Moreover, promising results have been obtained for BDNF in many experimental studies on animal models. In addition, BDNF serves as a crucial molecular target for developing drugs to treat neurological diseases. However, several pharmacokinetic difficulties have limited its use in clinical practice, such as its inability to cross the blood-brain barrier, short half-life, and potential adverse effects. To avoid these difficulties, several approaches have been explored, but they have led to disappointing results. One way to overcome the limitations of BDNF may be with mimetic molecules that can effectively stimulate the receptors it has an affinity with and thus activates BDNF pathways. In this perspective article, an evaluation of the efficacy of different BDNF mimetics against neurodegenerative diseases was made.
神经退行性疾病是一组慢性进行性疾病，其特征是由于神经元的结构和功能丧失，神经传递下降。虽然目前没有有效的神经退行性疾病治疗方法，但急需开发新的治疗策略。在神经营养因子中，BDNF 受到了广泛的研究，它已成为调节突触可塑性、神经元存活和分化的重要因子。在几种神经退行性疾病中，已经发现 BDNF 水平和信号通路发生了变化。此外，BDNF 在许多动物模型的实验研究中也取得了有希望的结果。此外，BDNF 是开发治疗神经疾病药物的重要分子靶点。然而，几种药代动力学困难限制了其在临床实践中的应用，例如它无法穿过血脑屏障、半衰期短和潜在的副作用。为了避免这些困难，已经探索了几种方法，但结果令人失望。克服 BDNF 局限性的一种方法可能是使用模拟分子，这些分子可以有效地刺激它具有亲和力的受体，从而激活 BDNF 途径。在这篇观点文章中，评估了不同 BDNF 模拟物对神经退行性疾病的疗效。
