Zuccato Chiara, Cattaneo Elena
Department of Pharmacological Sciences and Center for Stem Cell Research, University of Milan, via Balzaretti 9, Milan, Italy.
Nat Rev Neurol. 2009 Jun;5(6):311-22. doi: 10.1038/nrneurol.2009.54.
Changes in the levels and activities of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), have been described in a number of neurodegenerative disorders, including Huntington disease, Alzheimer disease and Parkinson disease. It is only in Huntington disease, however, that gain-of-function and loss-of-function experiments have linked BDNF mechanistically with the underlying genetic defect. Altogether, these studies have led to the development of experimental strategies aimed at increasing BDNF levels in the brains of animals that have been genetically altered to mimic the aforementioned human diseases, with a view to ultimately influencing the clinical treatment of these conditions. In this article, we will review the current knowledge about the involvement of BDNF in a number of neurodegenerative diseases, with particular emphasis on Huntington disease, and will provide the rationale for and discuss the problems in proposing BDNF treatment as a beneficial and feasible therapeutic approach in the clinic.
神经营养因子水平和活性的变化,如脑源性神经营养因子(BDNF),已在多种神经退行性疾病中被描述,包括亨廷顿病、阿尔茨海默病和帕金森病。然而,只有在亨廷顿病中,功能获得和功能丧失实验才从机制上将BDNF与潜在的基因缺陷联系起来。总之,这些研究促使了实验策略的发展,旨在提高那些经过基因改造以模拟上述人类疾病的动物大脑中的BDNF水平,以期最终影响这些病症的临床治疗。在本文中,我们将回顾关于BDNF参与多种神经退行性疾病的现有知识,尤其着重于亨廷顿病,并将阐述在临床上提出BDNF治疗作为一种有益且可行的治疗方法的基本原理及讨论其中存在的问题。