PDF(Pubmed)
Abstract：
In small clinical studies, the application of transcranial photobiomodulation (PBM), which typically delivers low-intensity near-infrared (NIR) to treat the brain, has led to some remarkable results in the treatment of dementia and several neurodegenerative diseases. However, despite the extensive literature detailing the mechanisms of action underlying PBM outcomes, the specific mechanisms affecting neurodegenerative diseases are not entirely clear. While large clinical trials are warranted to validate these findings, evidence of the mechanisms can explain and thus provide credible support for PBM as a potential treatment for these diseases. Tubulin and its polymerized state of microtubules have been known to play important roles in the pathology of Alzheimer\'s and other neurodegenerative diseases. Thus, we investigated the effects of PBM on these cellular structures in the quest for insights into the underlying therapeutic mechanisms. In this study, we employed a Raman spectroscopic analysis of the amide I band of polymerized samples of tubulin exposed to pulsed low-intensity NIR radiation (810 nm, 10 Hz, 22.5 J/cm2 dose). Peaks in the Raman fingerprint region (300-1900 cm-1)-in particular, in the amide I band (1600-1700 cm-1)-were used to quantify the percentage of protein secondary structures. Under this band, hidden signals of C=O stretching, belonging to different structures, are superimposed, producing a complex signal as a result. An accurate decomposition of the amide I band is therefore required for the reliable analysis of the conformation of proteins, which we achieved through a straightforward method employing a Voigt profile. This approach was validated through secondary structure analyses of unexposed control samples, for which comparisons with other values available in the literature could be conducted. Subsequently, using this validated method, we present novel findings of statistically significant alterations in the secondary structures of polymerized NIR-exposed tubulin, characterized by a notable decrease in α-helix content and a concurrent increase in β-sheets compared to the control samples. This PBM-induced α-helix to β-sheet transition connects to reduced microtubule stability and the introduction of dynamism to allow for the remodeling and, consequently, refreshing of microtubule structures. This newly discovered mechanism could have implications for reducing the risks associated with brain aging, including neurodegenerative diseases like Alzheimer\'s disease, through the introduction of an intervention following this transition.
摘要：
在小型临床研究中，经颅光生物调节（PBM）的应用，通常提供低强度近红外（NIR）来治疗大脑，在治疗痴呆症和几种神经退行性疾病方面取得了一些显著的成果。然而,尽管大量文献详细介绍了PBM结果背后的作用机制，影响神经退行性疾病的具体机制尚不完全清楚。虽然有必要进行大型临床试验来验证这些发现，机制的证据可以解释,从而为PBM作为这些疾病的潜在治疗提供可靠的支持.微管蛋白及其微管的聚合状态在阿尔茨海默病和其他神经退行性疾病的病理学中起重要作用。因此，我们研究了PBM对这些细胞结构的影响，以寻求对潜在治疗机制的见解。在这项研究中,我们对暴露于脉冲低强度近红外辐射（810nm，10Hz,22.5J/cm2剂量)。拉曼指纹区域（300-1900cm-1）中的峰-特别是，在酰胺I带（1600-1700cm-1）中，用于定量蛋白质二级结构的百分比。在这个乐队下,C=O拉伸的隐藏信号，属于不同的结构，叠加，因此产生复杂的信号。因此，为了可靠地分析蛋白质的构象，需要酰胺I带的准确分解。我们通过采用Voigt配置文件的简单方法实现了这一点。该方法通过未暴露对照样品的二级结构分析得到验证，可以与文献中的其他值进行比较。随后，使用这种经过验证的方法，我们提出了新的发现，在聚合NIR暴露的微管蛋白的二级结构有统计学意义的变化，与对照样品相比，其特征在于α-螺旋含量显着降低，β-折叠同时增加。这种PBM诱导的α-螺旋到β-折叠的转变与降低的微管稳定性和动力学的引入有关，以允许重塑和，因此,更新的微管结构。这种新发现的机制可能会对降低与大脑衰老相关的风险产生影响。包括神经退行性疾病，如阿尔茨海默病，通过在这一过渡之后引入干预措施。
