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      The Air We Breathe: Air Pollution as a Prevalent Proinflammatory Stimulus Contributing to Neurodegeneration

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          Abstract

          Air pollution is regarded as an important risk factor for many diseases that affect a large proportion of the human population. To date, accumulating reports have noted that particulate matter (PM) is closely associated with the course of cardiopulmonary disorders. As the incidence of Alzheimer’s disease (AD), Parkinson’s disease (PD), and autoimmune disorders have risen and as the world’s population is aging, there is an increasing interest in environmental health hazards, mainly air pollution, which has been slightly overlooked as one of many plausible detrimental stimuli contributing to neurodegenerative disease onset and progression. Epidemiological studies have indicated a noticeable association between exposure to PM and neurotoxicity, which has been gradually confirmed by in vivo and in vitro studies. After entering the body directly through the olfactory epithelium or indirectly by passing through the respiratory system into the circulatory system, air pollutants are subsequently able to reach the brain. Among the potential mechanisms underlying particle-induced detrimental effects in the periphery and the central nervous system (CNS), increased oxidative stress, inflammation, mitochondrial dysfunction, microglial activation, disturbance of protein homeostasis, and ultimately, neuronal death are often postulated and concomitantly coincide with the main pathomechanisms of neurodegenerative processes. Other complementary mechanisms by which PM could mediate neurotoxicity and contribute to neurodegeneration remain unconfirmed. Furthermore, the question of how strong and proven air pollutants are as substantial adverse factors for neurodegenerative disease etiologies remains unsolved. This review highlights research advances regarding the issue of PM with an emphasis on neurodegeneration markers, symptoms, and mechanisms by which air pollutants could mediate damage in the CNS. Poor air quality and insufficient knowledge regarding its toxicity justify conducting scientific investigations to understand the biological impact of PM in the context of various types of neurodegeneration.

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          Staging of brain pathology related to sporadic Parkinson’s disease

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            Stages in the development of Parkinson's disease-related pathology.

            The synucleinopathy, idiopathic Parkinson's disease, is a multisystem disorder that involves only a few predisposed nerve cell types in specific regions of the human nervous system. The intracerebral formation of abnormal proteinaceous Lewy bodies and Lewy neurites begins at defined induction sites and advances in a topographically predictable sequence. As the disease progresses, components of the autonomic, limbic, and somatomotor systems become particularly badly damaged. During presymptomatic stages 1-2, inclusion body pathology is confined to the medulla oblongata/pontine tegmentum and olfactory bulb/anterior olfactory nucleus. In stages 3-4, the substantia nigra and other nuclear grays of the midbrain and forebrain become the focus of initially slight and, then, severe pathological changes. At this point, most individuals probably cross the threshold to the symptomatic phase of the illness. In the end-stages 5-6, the process enters the mature neocortex, and the disease manifests itself in all of its clinical dimensions.
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              Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice.

              Parkinson's disease is characterized by abundant α-synuclein (α-Syn) neuronal inclusions, known as Lewy bodies and Lewy neurites, and the massive loss of midbrain dopamine neurons. However, a cause-and-effect relationship between Lewy inclusion formation and neurodegeneration remains unclear. Here, we found that in wild-type nontransgenic mice, a single intrastriatal inoculation of synthetic α-Syn fibrils led to the cell-to-cell transmission of pathologic α-Syn and Parkinson's-like Lewy pathology in anatomically interconnected regions. Lewy pathology accumulation resulted in progressive loss of dopamine neurons in the substantia nigra pars compacta, but not in the adjacent ventral tegmental area, and was accompanied by reduced dopamine levels culminating in motor deficits. This recapitulation of a neurodegenerative cascade thus establishes a mechanistic link between transmission of pathologic α-Syn and the cardinal features of Parkinson's disease.
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                Author and article information

                Contributors
                Journal
                Front Cell Neurosci
                Front Cell Neurosci
                Front. Cell. Neurosci.
                Frontiers in Cellular Neuroscience
                Frontiers Media S.A.
                1662-5102
                24 June 2021
                2021
                : 15
                : 647643
                Affiliations
                Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences , Krakow, Poland
                Author notes

                Edited by: Andrii Domanskyi, Orion Corporation (Finland), Finland

                Reviewed by: Katja Marika Kanninen, University of Eastern Finland, Finland; Mikko Airavaara, University of Helsinki, Finland

                *Correspondence: Monika Jankowska-Kieltyka jankow@ 123456if-pan.krakow.pl Irena Nalepa nfnalepa@ 123456cyf-kr.edu.pl

                Specialty section: This article was submitted to Cellular Neuropathology, a section of the journal Frontiers in Cellular Neuroscience

                Article
                10.3389/fncel.2021.647643
                8264767
                34248501
                837da74c-e207-41f6-b085-e644aeeff92c
                Copyright © 2021 Jankowska-Kieltyka, Roman and Nalepa.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 December 2020
                : 02 June 2021
                Page count
                Figures: 3, Tables: 0, Equations: 0, References: 206, Pages: 19, Words: 16658
                Funding
                Funded by: Narodowe Centrum Nauki 10.13039/501100004281
                Categories
                Cellular Neuroscience
                Review

                Neurosciences
                particulate matter,neurotoxicity,neuroinflammation,oxidative stress,neurodegeneration,autoimmunity

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