A specific fluorescent probe reveals compromised activity of methionine sulfoxide reductases in Parkinson's disease

Both chronic and acute neurodegenerative diseases have been associated with high morbidity and mortality, along with the death of neurons in different areas of the brain, and there are few or no effective curative therapy options for treatment of patients. [3,4] These disorders are a major cause of concern for the health and quality of life in the aging society, since age is the greatest risk factor for neurodegenerative disease. [5] The World Health Organization has predicted that in next 20 years neurodegenerative disease will become the second most common cause of mortality after cardiovascular disease. [6] Neurodegenerative processes begin long before their clinical symptoms are evident, and evolve for years slowly and irreversibly. Hence, there is an urgent need to diagnose neurodegenerative disease as early as possible and to distinguish between different neurodegenerative disorders with shared and unique symptoms to facilitate decision making regarding choice of treatment. Timely diagnosis is important for the adoption of therapeutic modalities in clinical trials prior to moderate dementia exhibition, to appraise and apply antidotes to maximally preserve the cognitive functions or to slow down the course of these disorders. The ability to analyze and identify risk factors for cognitive deficit would represent an extraordinary advancement in the field of dementia. [5] The main modern diagnostic technologies for the early examination of neurodegenerative disease pathology, neuroimaging techniques, include radioligandsbased positron emission tomography (PET), 3D single-photon emission-computed tomography (SPECT), and structural magnetic resonance imaging (MRI). Although PET and SPECT are the most used imaging techniques for neurodegenerative diseases, their application is limited by high cost, involvement of hazardous radiolabeled compounds, need for sophisticated instruments, and application of complex data acquisition and analysis protocols. The MRI technique has relatively low spatial resolution as well as intrinsically poor sensitivity to distinguish morphological differences between disease biomarkers and the surrounding tissue. Recently, fluorescence diagnosis technology has become an attractive and potential alternative to diagnose and probe the progression of neurodegenerative diseases, because of being rapid, noninvasive, sensitive, simple, real-time, low-cost, and high-resolution in nature. [7] There are several uses for Neurodegenerative diseases are debilitating disorders that feature progressive and selective loss of function or structure of anatomically or physiologically associated neuronal systems. Both chronic and acute neurodegenerative diseases are associated with high morbidity and mortality along with the death of neurons in different areas of the brain; moreover, there are few or no effective curative therapy options for treating these disorders. There is an urgent need to diagnose neurodegenerative disease as early as possible, and to distinguish between different disorders with overlap...

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Section: Parkinson's Diseasementioning

confidence: 99%

Fluorescent Diagnostic Probes in Neurodegenerative Diseases

et al. 2020

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“…Methionine oxidation is associated with the aging process and several pathophysiological conditions such as neurodegenerative diseases and cancer [ 64 , 65 ]. Previously, Met-SO formation under these conditions was regarded only as protein damage.…”

Section: Oxidative Modifications Of Sulfur Containing Residuesmentioning

confidence: 99%

Genetic Code Expansion: A Powerful Tool for Understanding the Physiological Consequences of Oxidative Stress Protein Modifications

Porter

Mehl

2018

Oxidative Medicine and Cellular Longevity

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Posttranslational modifications resulting from oxidation of proteins (Ox-PTMs) are present intracellularly under conditions of oxidative stress as well as basal conditions. In the past, these modifications were thought to be generic protein damage, but it has become increasingly clear that Ox-PTMs can have specific physiological effects. It is an arduous task to distinguish between the two cases, as multiple Ox-PTMs occur simultaneously on the same protein, convoluting analysis. Genetic code expansion (GCE) has emerged as a powerful tool to overcome this challenge as it allows for the site-specific incorporation of an Ox-PTM into translated protein. The resulting homogeneously modified protein products can then be rigorously characterized for the effects of individual Ox-PTMs. We outline the strengths and weaknesses of GCE as they relate to the field of oxidative stress and Ox-PTMs. An overview of the Ox-PTMs that have been genetically encoded and applications of GCE to the study of Ox-PTMs, including antibody validation and therapeutic development, is described.

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“…在细胞内, 蛋氨酸亚砜还原酶催化还原蛋氨酸亚砜是依赖硫氧还蛋白体系完成的, 在体外, 可以用 DTT替代硫氧还蛋白体系完成还原反应的循环. 在本课题组 [33] A可以催化还原探针Msr-TFMCM, 用于检测其活性. 同时 , 在固定酶和 DTT 的浓度条件下 , 改变探针的 http://engine.scichina.com/doi/10.1360/N032017-00053 浓度, 测定该探针在Msr A催化下的Vmax和Km值分别为3.78×10 −5 μM/s和3.94 μM.…”

Section: Msr-tfmcm对msr A的荧光响应unclassified

“…同时 , 在固定酶和 DTT 的浓度条件下 , 改变探针的 http://engine.scichina.com/doi/10.1360/N032017-00053 浓度, 测定该探针在Msr A催化下的Vmax和Km值分别为3.78×10 −5 μM/s和3.94 μM. 相比于Msr-blue [33] , 虽然 http://engine.scichina.com/doi/10.1360/N032017-00053…”

Section: Msr-tfmcm对msr A的荧光响应unclassified