Synaptic dysfunction in amyotrophic lateral sclerosis/frontotemporal dementia: Therapeutic strategies and novel biomarkers.
Synaptic dysfunction in amyotrophic lateral sclerosis/frontotemporal dementia: Therapeutic strategies and novel biomarkers.
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肌萎缩侧索硬化/额颞叶痴呆的突触功能障碍：治疗策略和新型生物标志物
DOI：
10.1002/jnr.24824
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发表时间：
2021-06
影响因子：
4.2
通讯作者：
Pasinelli P
中科院分区：
文献类型：
--
作者：
Krishnamurthy K;Pasinelli P
突触是神经系统中高度有序的信息中枢，突触前神经元和突触后神经元在这里进行交流（Sudhof; 2018）。突触的精确功能是由位于突触前和突触后神经元的蛋白质协调的有效神经传递来调节的（Margeta & Shen; 2010）。这些蛋白的失调会导致突触功能障碍，表现为神经元的高兴奋性或低兴奋性（Starr & Sattler; 2018, Jiang et al., 2019）。突触功能障碍是肌萎缩性侧索硬化症（ALS）和额颞叶变性（FTD）这两种神经退行性疾病的早期标志（Starr & Sattler; 2018, Ling; 2018, Yuyu Song; 2020），这两种疾病分别主要影响神经肌肉连接处和皮层突触。然而，最近的研究表明，ALS可能与一些患者的认知变化有关，临床上认为ALS- ftd （Saxon et al., 2017, Saxon et al., 2020）。在电生理学上，散发性和家族性ALS患者的运动神经元在病程早期表现为高兴奋性，随后在生命后期表现为低兴奋性（Vucic等人，2008，Bae等人，2013，Menon等人，2015）。然而，在FTD中观察到皮层的高兴奋性（Benussi et al., 2019）。为了更好地了解这些疾病背景下的突触功能障碍，有必要考虑RNA结合蛋白的蛋白质聚集的影响，如TAR dna结合蛋白43 （TDP-43）和融合肉瘤（FUS）。在FTD和ALS患者的脑和脊髓中观察到RNA结合蛋白TDP-43和FUS的细胞质蛋白聚集。（Blokhuis等人，2013，Balch等人，2008；Ling等人，2013，Taylor等人，2016）。有趣的是，突触蛋白质组在ALS和FTD中非常脆弱（Umoh等人，2018），这可能是由于病理蛋白聚集在蛋白酶体上的相互作用。在ALS的背景下，运动神经元的细胞生物学对* karthik提出了挑战。krishnamurthy@杰斐逊。Edu, krishnabio@ bgmail。com。作者的贡献
Synapses constitute highly organized informational hubs in the nervous system where a presynaptic and a postsynaptic neuron communicate (Sudhof; 2018). The precise functioning of the synapses is regulated by efficient neurotransmission orchestrated by proteins localized in the presynaptic and postsynaptic neurons (Margeta & Shen; 2010). Dysregulation of these proteins leads to synaptic dysfunction, manifesting itself as neuronal hyperexcitability or hypoexcitability (Starr & Sattler; 2018, Jiang et al., 2019). Synaptic dysfunction is an early hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD), two neurodegenerative disorders (Starr & Sattler; 2018, Ling; 2018, Yuyu Song; 2020), which predominantly affect the neuromuscular junction and cortical synapses, respectively. However, recent studies suggest that ALS may be associated with cognitive changes in some patients and is clinically considered as ALS-FTD (Saxon et al., 2017, Saxon et al., 2020). Electrophysiologically, motor neurons of both sporadic and familial ALS patients, exhibit hyperexcitability early in the disease course, followed by hypoexcitability later in life (Vucic et al., 2008, Bae et al., 2013, Menon et al., 2015). Whereas, cortical hyperexcitability is observed in FTD (Benussi et al., 2019). To better understand synaptic dysfunction in the context of these diseases, it is essential to consider the impact of protein aggregates of RNA binding proteins such as TAR DNA-binding protein 43 (TDP-43) and Fused in Sarcoma (FUS). Cytoplasmic protein aggregates of RNA binding proteins TDP-43 and FUS have been observed in the brain and spinal cord of FTD and ALS patients.(Blokhuis et al., 2013, Balch et al., 2008; Ling et al., 2013, Taylor et al., 2016). Interestingly, the synaptic proteome is extremely vulnerable in ALS and FTD (Umoh et al., 2018), perhaps due to the interplay of pathological protein aggregates on the proteasome. In the context of ALS, the cell biology of motor neurons poses challenges to* karthik. krishnamurthy@ jefferson. edu, krishnabio@ gmail. com. Author Contributions
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DOI：
10.1083/jcb.201302044
发表时间：
2013-04-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Li YR;King OD;Shorter J;Gitler AD
通讯作者：
Gitler AD
影响因子：
16.6
作者：
Casci, Ian;Krishnamurthy, Karthik;Pandey, Udai Bhan
通讯作者：
Pandey, Udai Bhan
影响因子：
3.5
作者：
Armstrong, Gary A. B.;Drapeau, Pierre
通讯作者：
Drapeau, Pierre
影响因子：
11
作者：
Saxon, Jennifer A.;Thompson, Jennifer C.;Snowden, Julie S.
通讯作者：
Snowden, Julie S.
影响因子：
12.7
作者：
Nizzardo, M.;Taiana, M.;Corti, S.
通讯作者：
Corti, S.