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第44卷第1期 李彦霖,王有民,朱 莉. miR⁃124在常见神经退行性疾病中的作用[J].
2024年1月 南京医科大学学报(自然科学版),2024,44(01):123-129 ·127 ·
因其重要的炎症介质作用成为潜在的抗炎治疗靶 [J]. N Engl J Med,2010,362(4):329-344
通路。过度活化的 NF⁃κB 信号通路被证实与 PD 的 [6] HANIU M,DENIS P,YOUNG Y,et al. Characterization
病理过程密切相关。Xing等 [58] 证实miR⁃124通过靶 of Alzheimer’s beta ⁃ secretase protein BACE. A pepsin
向调节 KPNB1、KPNA3 和 KPNA4 抑制 NF⁃κB 信号 family member with unusual properties[J]. J Biol Chem,
通路,参与 PD 的神经炎症过程。另一较为经典的 2000,275(28):21099-21106
[7] XIE H L,ZHAO Y,ZHOU Y,et al. MiR⁃9 regulates the
MAPK 信号通路参与细胞生长、分化以及炎症反应
expression of BACE1 in dementia induced by chronic
等多种细胞活动,p38 是 MAPK 家族成员之一,p38
brain hypoperfusion in rats[J]. Cell Physiol Biochem,
MAPK信号通路释放TNF⁃α和IL⁃1β等促炎因子,同
2017,42(3):1213-1226
时 p38 上调与自我吞噬相关的 p62 表达。Yao 等 [59]
[8] NELSON P T,WANG W X. MiR⁃107 is reduced in
发现在 MPTP 诱导的小鼠 PD 模型中,miR⁃124 通过 Alzheimer’s disease brain neocortex:validation study
靶向抑制p38和p62的表达减少促炎因子的释放和 [J]. J Alzheimer’s Dis,2010,21(1):75-79
自我吞噬。这些研究表明,miR⁃124 主要通过减少 [9] YANG G S,SONG Y M,ZHOU X Y,et al. MicroRNA⁃
促炎因子的释放等抑制炎症反应发挥神经保护作 29c targets β⁃site amyloid precursor protein⁃cleaving en⁃
用,提示miR-124有望成为治疗PD神经炎症的生物 zyme 1 and has a neuroprotective role in vitro and in vivo
靶点。 [J]. Mol Med Rep,2015,12(2):3081-3088
[10] ZHU H C,WANG L M,WANG M,et al. MicroRNA⁃195
3 小结与展望 downregulates Alzheimer’s disease amyloid⁃β production
by targeting BACE1[J]. Brain Res Bull,2012,88(6):
miR⁃124 在脑中高度表达,成为中枢神经系统
596-601
疾病的研究热点。miR⁃124可通过减少Aβ积累量,
[11] AN F,GONG G,WANG Y,et al. MiR⁃124 acts as a target
升高 ApoE 的表达,减少促炎因子的释放和增加抗
for Alzheimer’s disease by regulating BACE1[J]. Onco⁃
炎因子的释放在 AD 中发挥正向保护作用。在 PD target,2017,8(69):114065-114071
中 ,miR ⁃ 124 通 过 调 节 Bim、DAPK1、CAPN1 和 [12] SMITH P,AL HASHIMI A,GIRARD J,et al. In vivo regu⁃
ANXA5 等与自噬和神经元凋亡相关的靶基因对多 lation of amyloid precursor protein neuronal splicing by
巴胺能神经元起保护作用。基于以上miR⁃124在神 microRNAs[J]. J Neurochem,2011,116(2):240-247
经退行性疾病中的作用研究可以看出,miR⁃124 有 [13] OUYANG Q,LIU K,ZHU Q B,et al. Brain⁃penetration
望成为治疗神经退行性疾病的生物靶点;进一步研 and neuron⁃targeting DNA nanoflowers co⁃delivering miR⁃
究该分子在神经退行性疾病患者外周血中的表达 124 and rutin for synergistic therapy of Alzheimer’s dis⁃
ease[J]. Small Weinheim Der Bergstrasse Ger,2022,18
意义重大。
(14):e2107534
[参考文献] [14] LI A D,TONG L,XU N,et al. miR⁃124 regulates cerebro⁃
[1] LAGOS⁃QUINTANA M,RAUHUT R,YALCIN A,et al. microvascular function in APP/PS1 transgenic mice via
Identification of tissue ⁃ specific microRNAs from mouse C1ql3[J]. Brain Res Bull,2019,153:214-222
[J]. Curr Biol,2002,12(9):735-739 [15] WEINGARTEN M D,LOCKWOOD A H,HWO S Y,et al.
[2] BEN GACEM R,BEN ABDELKRIM O,ZIADI S,et al. A protein factor essential for microtubule assembly[J].
Methylation of miR⁃124a⁃1,miR⁃124a⁃2,and miR⁃124a⁃ Proc Natl Acad Sci USA,1975,72(5):1858-1862
3 genes correlates with aggressive and advanced breast [16] VOGELS T,MURGOCI A N,HROMÁDKA T. Intersec⁃
cancer disease[J]. Tumour Biol,2014,35(5):4047- tion of pathological tau and microglia at the synapse[J].
4056 Acta Neuropathol Commun,2019,7(1):109
[3] LU Y L,LIU Y,MCCOY M J,et al. MiR⁃124 synergism [17] MORTON H,KSHIRSAGAR S,ORLOV E,et al. Defec⁃
with ELAVL3 enhances target gene expression to promote tive mitophagy and synaptic degeneration in alzheimer’s
neuronal maturity[J]. Proc Natl Acad Sci USA,2021,118 disease:focus on aging,mitochondria and synapse[J].
(22):e2015454118 Free Radic Biol Med,2021,172:652-667
[4] KOZUKA T,OMORI Y,WATANABE S,et al. MiR⁃124 [18] 江泰君,朱凤亚,汤莉洁,等. 针刺治疗阿尔茨海默病的
dosage regulates prefrontal cortex function by dopaminer⁃ 机制[J]. 中国老年学杂志,2022,42(22):5667-5671
gic modulation[J]. Sci Rep,2019,9(1):3445 [19] JIA L F,ZHU M,YANG J W,et al. Prediction of p⁃tau/Aβ
[5] QUERFURTH H W,LAFERLA F M. Alzheimer’s disease 42 in the cerebrospinal fluid with blood microRNAs in Al⁃