School of Traditional Chinese Pharmacy, Yunnan University of Chinese Medicine, Yunnan 650500, China.
School of Basic Medical Sciences, Yunnan University of Chinese Medicine, Yunnan 650500, China.
Brain Res Bull. 2021 Jan;166:172-184. doi: 10.1016/j.brainresbull.2020.11.005. Epub 2020 Nov 14.
Brain-derived neurotrophic factor (BDNF) is involved in pathophysiological mechanisms in neuropsychiatric diseases, including depression, anxiety, and schizophrenia (SZ), as well as neurodegenerative diseases like Parkinson's disease (PD) and Alzheimer's disease (AD). An imbalance or insufficient pro-brain-derived neurotrophic factor (proBDNF) transformation into mature BDNF (mBDNF) is potentially critical to the disease pathogenesis by impairing neuronal plasticity as suggested by results from many studies. Thus, promoting proBDNF transformation into mBDNF is therefore hypothesized as beneficial for the treatment of neuropsychiatric and neurodegenerative diseases. ProBDNF is proteolytically cleaved into the mBDNF by intracellular furin/proprotein convertases and extracellular proteases (plasmin/matrix metallopeptidases). This article reviews the mechanisms of the conversion of proBDNF to mBDNF and the research status of intracellular/extracellular proteolytic proteases for neuropsychiatric and neurodegenerative disorders.
脑源性神经营养因子（BDNF）参与神经精神疾病的病理生理机制，包括抑郁症、焦虑症和精神分裂症（SZ），以及神经退行性疾病，如帕金森病（PD）和阿尔茨海默病（AD）。许多研究结果表明，脑源性神经营养因子前体（proBDNF）向成熟脑源性神经营养因子（mBDNF）的不平衡或不足转化可能对疾病的发病机制至关重要，因为这会损害神经元的可塑性。因此，促进 proBDNF 向 mBDNF 的转化被假设对神经精神疾病和神经退行性疾病的治疗有益。proBDNF 通过细胞内弗林/蛋白原转化酶和细胞外蛋白酶（纤溶酶/基质金属蛋白酶）切割成 mBDNF。本文综述了 proBDNF 向 mBDNF 转化的机制以及细胞内/细胞外蛋白水解蛋白酶在神经精神疾病和神经退行性疾病中的研究现状。
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