Lysophospholipids-potent candidates for brain food, protects neuronal cells against α-Synuclein aggregation
Lysophospholipids-potent candidates for brain food, protects neuronal cells against α-Synuclein aggregation
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溶血磷脂是大脑食物的有效候选者，可保护神经细胞免受 α-突触核蛋白聚集
DOI：
10.1016/j.biopha.2022.113891
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Tsukahara Tamotsu
中科院分区：
文献类型：
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作者：
Karaki Tatsuya;Haniu Hisao;Matsuda Yoshikazu;Tsukahara Tamotsu
α-突触核蛋白（α-Syn）的积聚和聚集是α-突触核蛋白病（包括路易体痴呆（LB））发生的标志。预期聚集抑制剂可降低α-Syn毒性并用作治疗剂。因此，α-Syn被认为是药物开发的潜在和优先目标。在这里，我们报告了抑制α-Syn聚集的某些溶血磷脂（LPLs）的物种。LPL是具有生物活性的小脂质分子，其特征是单个碳链和极性头基。这里使用的LPL是从猪肝分解产物（PLDP）中提取的，该产物先前被报道可以增强健康老年人的认知功能。在这项研究中，我们发现PLDP提取的脂质（PEL）减少了细胞模型中的α-Syn聚集。特别地，发现已知包含在PEL中的溶血磷脂酰胆碱（LPC）16：0、LPC 18：0、LPC 18：1和溶血磷脂酰乙醇胺（LPE）16：0强烈抑制α-Syn聚集。此外，当α-Syn与LPL共孵育时，Thioflavin-T（ThT）的荧光发射显著下降，表明纤维形成较低。有趣的是，在每种LPL中观察到对不溶性α-Syn还原的影响程度存在差异。在这种情况下，LPC 18：1和LPE 18：1似乎在体外与低于1 nM的α-Syn相互作用。总之，这些研究表明PLDP衍生的LPL作为针对α-突触核蛋白病的有效治疗剂的潜力。
Accumulation and aggregation of α-Synuclein (α-Syn) are the hallmarks of the incidence of α-Synucleinopathies, which comprises dementia with Lewy bodies (LBs). Aggregation inhibitors are anticipated to reduce α-Syn toxicity and serve as therapeutic agents. As a result, α-Syn is regarded as the potential and priority target for drug development. Here, we report inhibition of α-Syn aggregation by a certain lysophospholipids (LPLs) species. LPLs are small bioactive lipid molecules characterized by a single carbon chain and polar head group. The LPLs used here were extracted from porcine liver decomposition product (PLDP), which was previously reported to enhance cognitive function in healthy older adults. In this study, we found that PLDP-extracted lipids (PEL) reduced α-Syn aggregation in a cellular model. In particular, lysophosphatidylcholine (LPC) 16:0, LPC18:0, LPC18:1, and lysophosphatidylethanolamine (LPE) 16:0, which are known to be contained in PEL, were found to strongly inhibit α-Syn aggregation. Furthermore, when α-Syn was co-incubated with LPLs, the fluorescence emission of Thioflavin-T (ThT) declined remarkably, indicating a lower fibril formation. Interestingly, differences were observed in the degrees of effect on the reduction of insoluble α-Syn among each LPL. In this context, LPC18:1 and LPE18:1 appeared to interact with α-Syn below 1 nM in vitro. Taken together, these studies indicated the potential of PLDP-derived LPLs as effective therapeutic agents against α-Synucleinopathies.