阿尔茨海默病（AD）是一种常见的神经退行性疾病，占全球痴呆病例的 50% 以上，其最常见的症状包括语言障碍，学习、记忆能力下降，情绪波动大，行为 能力丧失等，严重影响全球数千万人的生活。阿尔兹海默病起病隐袭，且病情会 随时间的推移不断恶化，患者随着身体功能的逐渐丧失最终走向死亡。在此过程 中患者在面对病痛折磨的同时还需要终身照护，这无疑给患者及其家庭以及社会 都带来了沉重的精神及经济负担。 

       阿尔茨海默病的发生与环境、遗传等多种复杂因素相关，导致其致病机理存 在多种假说。其中 Aβ 蛋白病理性沉积构成的蛋白聚集体及 Tau 蛋白过度磷酸化 病理性聚集造成的神经元纤维缠结（NFT）所产生的神经毒性是目前普遍认可的 两种机理，相应微观机制仍需深入研究。但有效抑制和调控有害蛋白聚集体和纤 维化的形成是阿尔兹海默病等神经退行性疾病治疗以及药物开发的重要方向。

       目前神经退行性疾病的药物治疗有很大局限性，只能暂时延缓症状，不能逆 转疾病进程，且服药后会伴随各种严重的副作用，因此非侵入性的多种物理治疗 方式逐步得到重视。与传统的药物治疗相比，激光治疗具有光毒性低、选择性好、 不侵入、可消灭隐性病灶等优点，可能动地调控蛋白结构变化动力学，从而提供 了体外调控蛋白聚集的新策略。尤其近年来发展起来被称为生命之光的太赫兹 （THz）光，其光子能量低、穿透深度大，且能量范围对应于生物大分子骨架振 动、转动以及分子间氢键等弱相互作用，可无损性地与生物大分子、生物个体在 多个层次上发生生物效应。

       因此，本文尝试用 THz 光场照射的方式来调控聚集 蛋白解聚动力学，以期为神经退行性疾病研究提供新的视角和方案。 在本论文中，我们首先以细胞骨架肌动蛋白丝（F-actin）为模型蛋白模拟阿 尔兹海默病患者脑内的不溶性蛋白聚集体，利用超高时间分辨性红外光谱和超分 辨成像技术，分别在细胞及蛋白分子水平研究了生理环境下 A549 细胞骨架肌动 蛋白丝在 THz 光照射作用下的结构变化动力学。结果表明，实验组细胞及蛋白 与对照组之间具有显著的统计学差异，在不破坏蛋白骨架的情况下，THz 光可共 振性地与细胞及蛋白直接发生相互作用，可解聚纤维化肌动蛋白丝，使丝状聚集 体蛋白向单体蛋白方向转化。在此基础上，我们对神经退行性疾病紧密相关的 Tau 神经蛋白进行了进一步研究，初步看到了与 actin 蛋白类似的结果。此结果 首次清晰地揭示了 THz 光源可用于调控神经蛋白纤维化动力学。从而表明 THz 光场可为神经退行性疾病研究和治疗提供一种无损、不侵入的新思路和新型手段。

       Alzheimer's disease (AD) is a common neurodegenerative disease, accounting for more than 50% of dementia cases worldwide, and its most common symptoms include language disorders, decreased learning and memory ability, mood swings, and loss of behavioral capacity, which seriously affect the lives of tens of millions of people around the world. Alzheimer's disease begins imperceptible and worsens over time, eventually dying as the patient loses function. In this process, patients need lifelong care while facing the torment of illness, which undoubtedly brings a heavy mental and economic burden to patients, their families and society.

        The occurrence of Alzheimer's disease is related to a variety of complex factors such as environment and genetics, resulting in a variety of hypotheses about its pathogenic mechanism. Among them, the neurotoxicity caused by protein aggregates composed of pathological deposition of Aβ protein and neuronal fiber tangles (NFT) caused by excessive phosphorylation of tau protein are two widely recognized mechanisms, and the corresponding microscopic mechanisms still need to be studied in depth. However, effectively inhibiting and regulating the formation of harmful protein aggregates and fibrosis is a reasonable direction for the treatment of neurodegenerative diseases such as Alzheimer's disease and drug development.

       At present, the drug treatment of neurodegenerative diseases has great limitation. It can only temporarily delay the symptoms, but cannot reverse the disease process. After taking the drug, it will be accompanied by various serious side effects. Therefore, various non-invasive physical therapy methods have gradually received attention. Compared with traditional drug therapy, laser therapy has the advantages of low phototoxicity, good selectivity, non-invasiveness, and the ability to eliminate hidden lesions. It may dynamically regulate the dynamics of protein structure changes, thus providing a new strategy for regulating protein aggregation in vitro. In particular, terahertz (THz) light, which has been developed in recent years and is called the light of life, has low photon energy and a large penetration depth, and its energy range corresponds to the weak interactions such as the vibration and rotation of biological macromolecular skeletons and intermolecular hydrogen bonds, can produce biological effects on multiple levels with biological macromolecules and biological individuals without damage.

      Therefore, this paper tries to regulate the disaggregation kinetics of aggregated proteins by THz light field irradiation, in order to provide new perspectives and solutions for the treatment of neurodegenerative diseases. In this paper, we first used cytoskeletal actin filaments (F-actin) as a model protein to simulate insoluble protein aggregates in the brain of Alzheimer's disease patients, and used ultra-high time-resolution infrared spectroscopy and super-resolution imaging technology to study the structural change dynamics of A549 cytoskeletal actin filaments with THz irradiation under the physiological environment at the cellular and protein molecular levels, respectively. The results showed that there were significant statistical differences between cells and proteins in the experimental group and the control group, and without destroying the protein skeleton, THz light could resonantly interact directly with cells and proteins, which could depolymerize fibrotic actin filaments and transform filamentous aggregates proteins into monomeric proteins. On this basis, we conducted further research on the tau neuro-protein closely related to neurodegenerative diseases, and initially saw similar results to the actin protein. This result clearly reveals for the first time that THz light sources can be used to regulate neuro-protein fibrosis dynamics. This shows that THz light field can provide a new idea and new method for non-destructive and non-invasive treatment of neurodegenerative diseases.