-Synuclein, a presynaptic neuronal protein encoded by the gene, is involved in the pathogenesis of Parkinson’s disease. Point mutations and multiplications of -synuclein (A30P and A53T) are correlated with early-onset Parkinson’s disease characterized by rapid progression and poor prognosis. Currently, the clinical identification of variants, especially disease-related A30P and A53T mutants, remains challenging and also time consuming. This study aimed to develop a novel label-free detection method for distinguishing the mutants using transmission terahertz (THz) time-domain spectroscopy. The protein was spin-coated onto the quartz to form a thin film, which was measured using THz time-domain spectroscopy. The spectral characteristics of THz broadband pulse waves of -synuclein protein variants (SNCA wild type, A30P, and A53T) at different frequencies were analyzed via Fourier transform. The amplitude A intensity (A, A, and A) and peak occurrence time in THz time-domain spectroscopy sensitively distinguished the three protein variants. The phase difference in THz frequency domain followed the trend of > > . There was a significant difference in THz frequency amplitude A′ corresponding to the frequency ranging from 0.4 to 0.66 THz (A′ > A′ > A′). At a frequency of 0.4–0.6 THz, the transmission T of THz waves distinguished three variants (T > T > T), whereas there was no difference in the transmission T at 0.66 THz. The SNCA wild-type protein and two mutant variants (A30P and A53T) had distinct characteristic fingerprint spectra on THz time-domain spectroscopy. This novel label-free detection method has great potential for the differential diagnosis of Parkinson’s disease subtypes.

中文翻译：

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太赫兹时域光谱上α-突触核蛋白突变体的特征指纹图谱

-突触核蛋白是该基因编码的一种突触前神经元蛋白，参与帕金森病的发病机制。 β-突触核蛋白（A30P 和 A53T）的点突变和增殖与早发性帕金森病相关，其特征是进展迅速和预后不良。目前，变异体，特别是与疾病相关的 A30P 和 A53T 突变体的临床鉴定仍然具有挑战性且耗时。本研究旨在开发一种新型无标记检测方法，利用透射太赫兹（THz）时域光谱来区分突变体。将蛋白质旋涂在石英上形成薄膜，并使用太赫兹时域光谱进行测量。通过傅里叶变换分析不同频率下α-突触核蛋白变体（SNCA野生型、A30P和A53T）的太赫兹宽带脉冲波的光谱特征。太赫兹时域光谱中的振幅 A 强度（A、A 和 A）和峰值出现时间可以灵敏地区分三种蛋白质变体。太赫兹频域相位差呈现>>的趋势。 0.4~0.66 THz频率范围内的太赫兹频率振幅A′存在显着差异（A′>A′>A′）。在0.4-0.6 THz频率下，太赫兹波的传输Tg区分了三种变体（T > T > T），而0.66 THz的传输Tg没有差异。 SNCA 野生型蛋白和两个突变体（A30P 和 A53T）在太赫兹时域光谱上具有明显的特征指纹图谱。这种新颖的无标记检测方法对于帕金森病亚型的鉴别诊断具有巨大的潜力。