Activation of cellular and molecular mechanisms involved in Alzheimer's disease by PM 2.5 particles in the air of Tehran city

24 August 2022 | 12:20
The new research of University of Tehran researchers shows the induction of multiple cellular and molecular processes related to Alzheimer's disease and other neurodegenerative diseases by fine particles suspended in the air of Tehran city known as PM 2.5 and as a result of their destructive effects on proteins and nerve cells
Activation of cellular and molecular mechanisms involved in Alzheimer's disease by PM 2.5 particles in the air of Tehran city

According to the public relations report of the University of Tehran, quoted by the Faculty of Science, this study, which is in the form of a doctoral dissertation by Zahra Khoshkam in the Protein Biotechnology Research Laboratory (PBRL), School of Biology, College of Science,  University of Tehran, with the guidance of Dr. Mehran Habibi Rezaei and Dr. Ali Akbar Mousavi Mohadi and the cooperation of the Research Center air pollution of Tehran University of Medical Sciences has been done, it was able to identify the destructive effects of air pollution in Tehran city in inducing multiple cellular and molecular mechanisms involved in Alzheimer's disease.

The findings of this research specifically indicate the major role of suspended fine particles (PM 2.5) as the most dangerous pollutant in the air of polluted cities, in inducing hypoxia as one of the main and common risk factors in the occurrence of neurodegenerative diseases.
According to this report, the concentration of PM 2.5 particles collected in the city of Tehran, especially in cold seasons, increases to an alarming extent, six to seven times compared to the maximum standard declared by the World Health Organization (WHO) for long-term exposure to these particles. . Therefore, residents of cities with polluted air like Tehran are at serious risk of suffering from brain diseases caused by long-term inhalation of these particles, especially the increase of Alzheimer's disease.
According to these researchers, more than 95% of the cases of Alzheimer's disease, as the most common neurodegenerative disease, are diagnosed with this disease without having a genetic history and mainly due to the influence of environmental factors and pollutants at the age of 65. Several years before the appearance of symptoms of forgetfulness or dementia as the most obvious complication in Alzheimer's patients, cellular and molecular processes related to the death of nerve cells, including the increase of toxic accumulations of amyloid-beta peptide and fibrillar aggregates of protein tau (tau) begin in the brain. Therefore, it is important to determine the cellular and molecular mechanisms involved in the occurrence of this disease in order to adopt prevention and treatment measures.
Based on the comprehensive chemical analysis of collected PM 2.5 particles, these particles contain various elements and metals, including heavy and transition metals, as well as organic compounds such as polyaromatic hydrocarbons (PAH) with very high oxidation capability and the ability to induce oxidative stress in cells of nervous tissue.
Among the other very important findings of this research team is showing the effect of PM 2.5 particles in increasing the expression of beta-secretase enzyme as one of the main enzymes involved in the increase of amyloid plaques in the brain, along with increasing the induction of endoplasmic reticulum stress, which can result in the increase Oxidative stress occurs due to the presence of particles in cells or the intracellular activation of the aryl hydrocarbon receptor (AHR) and the reduction of HIF1α protein activity, which plays a key role in the hypoxia process.
Also, the findings of this research indicate the increase of oxidative stress damages on lipids and cell proteins, the induction of cell hypoxia and their destructive effects on hemoglobin protein, and as a result, the reduction of oxygen supply to the brain. The results of this research specifically showed that the expression of hypoxia-fighting genes and proteins in nerve cells, such as HIF1α protein and the oxygen-storing protein in nerve cells called neuroglobin, both of which play a protective role in nerve cells, with an increase in the concentration of PM 2 particles. 5 in cell culture studies show a significant decrease compared to untreated cells.
According to the obtained results, it can be said that the activation of the AHR receptor by PM 2.5 particles, which increases the expression of foreign compound metabolizing proteins such as Cyp1a1 and Cyp1E2, with the activity of copying genes under its control, causes the production of more dangerous and toxic secondary compounds. As a result, the activation of this receptor increases the production of ROS and endoplasmic reticulum stress in cells, followed by cell death. On the other hand, with the activation of AHR, the level of expression and activity of HIF1α and neuroglobin proteins in cells exposed to particles also decreases, which leads to a decrease in the ability of cells to cope with oxidative stress induced by particles
The researches of this research team for the first time in the world by conducting various studies with biochemistry-biophysics approaches on the hemoglobin protein showed that this protein undergoes oxidative damage and its structure is damaged in long-term and short-term exposure to PM 2.5 particles. It was also shown that with the oxidation of the prosthetic group in the presence of PM 2.5 oxidative particles, the performance of the protein in the ability to carry oxygen is greatly reduced, and then the formation of methemoglobin increases.
Following these events, finally, with the release of the heme group, the destruction of the hemoglobin protein also occurs, which is consistent with the results of various epidemiological studies conducted in Peru, China, and Thailand, which showed the effect of exposure to PM 2.5 particles in increasing anemia and decreasing The concentration of hemoglobin in the blood of a large population of people has been examined. Non-enzymatic destruction of heme group by PM 2.5 particles in neuroglobin proteins and cytochrome of nerve cells can lead to the induction of Alzheimer's disease pathogenesis caused by brain hypoxia.
The preliminary results of this research have been published in volume 810 of the prestigious journal Science of Total Environment