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The latest research from NSYSU reveals the molecular pathological mechanisms that cigarette aerosol may aggravate the course of Parkinson's disease

2024-07-09

 

People with a family history of Parkinson's disease should stay away from second-hand smoke! The cross-disciplinary research team of the Aerosol Science Research Center (ASRC) of National Sun Yat-sen University (NSYSU), led by the Director of the center and Professor of the Department of Chemistry, Chia C. Wang, and Professor Hsiu-Fang Fan of the Institute of Medical Science and Technology, carried out joint research and found that the aerosols, suspended particles in the smoke released when cigarettes are burned, more than 80% of suspended particles  have a diameter smaller than 1 micron (μm) (thus termed PM1), making them incredibly harmful to health and may aggravate the course of Parkinson's disease. The results were published in the internationally renowned journal, ACS Chemical Neuroscience.

 

There are many potential sources of aerosols in our living environments, encompassing from natural aerosols such as ocean droplets, biomass burning, volcanoes, pollen, and spore aerosols to various air pollution emissions in the industrial society. Aerosols from different sources exhibit different chemical compositions and particle sizes. Chia C. Wang, Director of the ASRC of NSYSU, pointed out that while aerosol is a general term for fine particles suspended in the air, PM2.5, with a particle size of less than 2.5 μm, is the most well-known. The mixed smoke released when cigarettes burn contains many aerosol particles, which are also the essential components of second-hand smoke. "During the collection of cigarette aerosol, it was found that more than 80% by weight of cigarette aerosol belong to PM1 (particulate matter with a particle size of less than 1 μm) ultrafine particles."

 

Chia C. Wang stressed that after aerosol particles of different sizes enter the human body through breathing, they may deposit at various parts of the respiratory system based on their particle size and other physical and chemical properties. Larger particles (above 10 μm) are usually deposited in the upper respiratory tract, while smaller particles have a greater chance of entering deeper into the lungs and depositing in the lower respiratory tract or even the alveolar area. After entering the human body, some PM1 may even penetrate the alveoli, enter the blood circulatory system and affect other organs, or penetrate the blood-brain barrier from the olfactory bulb area through the olfactory pathway, enter the central nervous area of the brain, affect the operation of brain nerve cells, and even cause neurodegenerative diseases, or aggravate the course. General medical masks cannot effectively filter out PM2.5 or even PM1 particles.

 

Parkinson's disease is the most common neurodegenerative disease after Alzheimer's disease. Many studies have found that Parkinson's disease is related to the misfolding and formation of aggregation of α-Synuclein (α-Syn) in the brain, which can lead to impaired nerve cell function or even death. Hsiu-Fang Fan, a professor at the Institute of Medical Science and Technology at NSYSU, said that the team used SH-SY5Y, a neuroblastoma cell line, overexpressing α-Syn,  generally accepted as a Parkinson's disease cell model. After treating cells with collected and extracted cigarette aerosols according to different particle size ranges, the oligomerization of α-Syn and cell survival rate of SH-SY5Y cells were affected. Normal α-Syn exists in a tetrameric form, but under oxidative stress, structural changes occur, forming stacked oligomers in punctate distributions in cells, accompanied by a reduction in autophagy activity. Suppose the clearing capacity of autophagic activity of cells is reduced, or a large number of stacked proteins are produced that cannot be cleared in time and accumulate in the cells, causing increased toxicity and leading to damage to nerve cell function and death. In that case, the deposits released could also be swallowed up by neighboring cells and die together, forming a vicious cycle.

 

Hsiu-Fang Fan further pointed out that the research team used self-built Fluorescence Cross-Correlation Spectroscopy (FCCS) to observe that the combination of α-Syn and cigarette aerosol components aggravated the symptoms caused by cigarette aerosol extract-induced intracellular cytotoxicity, oxidative stress, mitochondrial dysfunction, and autophagy dysregulation ultimately leading to elevated cell mortality in SH-SY5Y cells overexpressing α-Syn, a cellular model of Parkinson's disease. Compared with previous research, which mostly focused on the effects of outdoor air pollution aerosols on neurodegenerative diseases, the NSYSU ASRC research team revealed for the first time the important components in second-hand smoke, providing new insight of the pathological effects of cigarette aerosols of varying sizes on α-Syn. The study provides new insights into the molecular mechanisms of their impact on neurodegenerative diseases and also highlights the importance of ultrafine suspended particles in air pollution on the course, development, and management of neurodegenerative diseases.

 

The research team stated that although some previous literature indicated that nicotine can reduce the incidence of Parkinson's disease or alleviate and inhibit the course of the disease, the results of this study show that if the human body is exposed to second-hand smoke, it will indeed increase neurotoxicity and facilitate cell death in cellular Parkinson's disease model. The research team also reminds three high-risk groups, including patients with Parkinson's disease, those with a family history of early-onset Parkinson's disease, and those with abnormal late-night schedules, to avoid smoking or being exposed to second-hand smoke to reduce the risk of disease. In addition, taking antioxidants and exercising regularly can increase the antioxidant capacity in cells and slow down the damage that may be caused by oxidative stress.

 

Journal link: https://pubs.acs.org/doi/epdf/10.1021/acschemneuro.3c00771

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