|Year : 2018 | Volume
| Issue : 1 | Page : 4-7
Particulate air pollution and neurological diseases: The role of tauopathies
Hsiao-Chi Chuang1, Dean Wu2, Jiunn-Horng Kang3
1 School of Respiratory Therapy, College of Medicine, Taipei Medical University; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei; Department of Internal Medicine, Division of Pulmonary Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
2 Department of Neurology, Shuang Ho Hospital, Taipei Medical University; Sleep Center, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
3 Department of Physical Medicine and Rehabilitation, Taipei Medical University Hospital, Taipei; Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
|Date of Submission||20-Dec-2017|
|Date of Acceptance||07-Mar-2018|
|Date of Web Publication||11-Apr-2018|
Dr. Hsiao-Chi Chuang
Taiwan Cardiopulmonary Research Group, School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei
Source of Support: None, Conflict of Interest: None
Neurodegenerative diseases, such as dementia, Parkinson's disease, and parkinsonism, are due to the gradual and progressive loss of neural cells, leading to nervous system dysfunction. Increasing epidemiological and toxicological evidence has demonstrated the possible association between neurological diseases and particulate air pollution. Chronic exposure to particulate matter (PM) of <2.5 μm in aerodynamic size (PM2.5) is related to reductions in white matter and gray matter in brains of older women. Alterations of the structural integrity of the brain were reported for particulate air pollution-induced neurological disorders. Clinically, intraneuronal accumulation of tau proteins is considered to be an important hallmark of the development of neurodegenerative diseases. In Alzheimer's disease brains, for example, hyperphosphorylated levels of tau are around 3–4 times higher than levels in normal adult brains. Tau overexpression in neuroblastoma cells can lead to tau aggregations and the appearance of smaller proteolytic fragments. Degradative mechanisms, such as autophagy that remove tau from cells are considered essential functions for maintaining the brain's health. Notably, increasing numbers of reports have indicated that autophagy dysfunction occurs due to particulate air pollution in vitro and in vivo. Dysfunction of autophagy can lead to tau accumulation in the brain. We reviewed the effects of particulate air pollution on neurological diseases and the underlying mechanisms (i.e., tau and autophagy). Further toxicological evidence is required to fill in the gaps between epidemiological and clinical observations.
Keywords: Autophagy, central nervous system, neurological disorder, particulate matter, tau
|How to cite this article:|
Chuang HC, Wu D, Kang JH. Particulate air pollution and neurological diseases: The role of tauopathies. Environ Dis 2018;3:4-7
| Neurological Disorders|| |
The National Institute of Neurological Disorders and Stroke reported that there are more than 600 neurological disorders, with approximately 50 million Americans affected each year. This suggests that neurological disorders are important public health issues now. Neurodegenerative diseases, such as dementia, Parkinson's disease (PD), and Parkinsonism More Details, are due to the gradual and progressive loss of neural cells, leading to central nervous system (CNS) dysfunction. PD, for example, is a progressive neurodegenerative disorder. The progression rate of mild cognitive dysfunction due to PD to PD dementia is approximately 60% over a period of 4 years. Mild cognitive dysfunction is a prodromal syndrome of neurodegenerative dementia without significant dysfunction in activities of daily living (ADLs). Notably, mild cognitive dysfunction is unspecific, as it can occur due to various diseases. Definitions of mild cognitive impairment include (1) memory complaints, preferably corroborated; (2) normal general cognitive functions; (3) normal performance of ADLs; (4) impaired memory in relation to age and education; and (5) a lack of dementia. Increasing evidence has shown that mild cognitive dysfunction is a transitional state between normal aging and neurodegenerative disease.
| Air Pollution and Neurological Disorders|| |
A growing body of epidemiological and clinical evidence has led to heightened concerns about the potential deleterious effects of ambient air pollution on human health. Particulate air pollutants (e.g., particulate matter [PM] of <2.5 μm in aerodynamic diameter [PM2.5]) are associated with increased hospital admissions and mortality due to pulmonary and cardiovascular diseases.,, Air pollutants facilitate the development of pulmonary diseases by interfering with nonspecific and specific lung defenses. The increased risk of cardiovascular disease due to PM exposure was reported by the American Heart Association. A study of hospital admission rates in 1999–2002 for cardiovascular and respiratory outcomes and injuries in the United States (US) found a 1.28% increase in the risk of heart failure per 10 μg/m 3 in same day PM2.5 exposure. Deaths due to arrhythmias, heart failure, and cardiac arrest were associated with long-term exposure to PM. Daily hospitalizations for heart failure were also associated with short-term changes in PM exposure. Chronic air pollution exposure is also associated with an increased risk of atherosclerosis. Künzli et al. showed that increases of 10 and 20 μg/m 3 in PM10 (PM of ≤10 μm in aerodynamic diameter) were respectively associated with 5.9% and 12.1% increases in the development of atherosclerosis.
Accumulating epidemiological evidence indicates that pulmonary exposure to particulate air pollution is associated with neurological disorders such as loss of cognition and depression. Exposure to traffic-related pollution and black carbon was related to reductions in cognition function in older men. Notably, neurological disorders were related to exposure to different size fractions of particulate air pollution. For example, exposure to high levels of coarse PM (PM2.5–10) and fine PM (PM2.5) was related to faster cognitive declines as reported by the Nurses' Health Study Cognitive Cohort in the US. Exposure to PM10 was associated with symptoms of depression in elderly adults in a Korean study. A previous report observed that long-term exposure to PM2.5 was associated with depression onset in middle-aged and older women. These epidemiological associations point out that particulate air pollution may be a risk factor for the onset and progression of neurological disorders, especially in aging populations.
| Association of Particulate Air Pollution With the Brain's Structure|| |
Although particulate air pollution has been linked to neurological disorders, only a few studies have begun to examine pathophysiological changes caused by particulate air pollution. The Framingham Offspring Study found that elevated exposure levels to PM2.5 were associated with smaller total cerebral brain volumes. Chen et al. reported similar findings of older women with high levels of PM2.5 exposure having significantly smaller white matter volumes in the Women's Health Initiative Memory Study. They further showed that smaller white matter volumes were present in the frontal and temporal lobes and corpus callosum, but not in the hippocampus. Results from the same cohort study indicated that long-term PM2.5 exposure might accelerate loss of both white matter and gray matter in older women. Alterations of the structural integrity of the brain could be hallmarks of pathophysiological changes of particulate air pollution-induced neurological disorders; however, further studies need to examine the possible mechanisms.
| Air Pollution and Central Nervous System Neuroinflammation|| |
Experimental studies observed that exposure to diesel exhaust particles (DEPs) altered motor activity, spatial learning and memory, the novel object recognition ability, and emotional behavior in the CNS.,, Neuroinflammation, a nonspecific protective response, is recognized as a critical step in the response to exposure to particulate air pollution by removing injurious stimuli and initiating the healing process., Chronic inflammation was observed in aged brains, whereas there is a further increase in brain inflammation in neurodegenerative disorders. Increasing numbers of studies have observed that exposure to particulate air pollution is able to provoke neuroinflammation. Costa et al. indicated that acute exposure to high levels of DEPs (250–300 μg/m 3) for 6 h induced oxidative stress, microglia activation, neuroinflammation, and neurogenesis impairment in various brain regions such as the hippocampal subgranular zone and subventricular zone. Campbell et al. observed that asthmatic mice exposed to concentrated ambient particles exhibited increased inflammatory cytokines, such as interleukin-1α and tumor necrosis factor-α in brain tissues. Guerra et al. further showed that exposure to different size fractions of ambient particles caused distinct physiological changes, inflammation, oxidative stress, and unfolded protein responses in the CNS, particularly in the striatum. Although in vivo studies indicated that particulate air pollution causes neuroinflammation, possible lung-to-brain pathways of particle exposure remain unclear. In the specific case of particulate air pollution, a number of parameters were directly linked to particle-induced lung inflammation, specifically the particle burden and oxidative stress., Notably, previous studies showed that nanoparticles (<100 nm) are capable of being translocated to the brain through olfactory nerves. Furthermore, inhaled particulate air pollution may directly and/or indirectly induce brain inflammation from the lungs to the brain. Notably, a study observed that exposure to traffic-related air pollution altered the brain's microvascular integrity in a high-fat diet animal model. That observation suggests that particulate air pollution can cause blood–brain barrier impairment, leading to local inflammation due to particle accumulation in the brain.
| Autophagy and Air Pollution-Driven Oxidative Damage|| |
Oxidative damage to surrounding tissues leads to the formation of highly reactive organic molecules that can nonenzymatically modify proteins and that target-specific peptide residues containing lysine, arginine, cysteine, or histidine. In biological systems, soluble proteins and small soluble protein aggregates are degraded by proteasomes, whereas insoluble aggregates are sequestered into inclusion bodies or microtubule-associated aggresomes, and disposal of these aggregates occurs through the autophagic process through the lysosomal pathway. Autophagy is initiated at the isolation membrane (the so-called phagophore), and coordinated actions of autophagy-related (Atg) proteins result in expansion of this membrane to form the autophagosome. Ubiquitination functions as a general tag for the selective autophagy of mammalian cells. Ubiquitin-like protein conjugation systems regulate phagophore expansion. For example, Atg8 is processed by the Atg4 protease at its C-terminal amino acid(s), is activated by Atg7, and is conjugated to phosphatidylethanolamine by Atg3. Autophagy receptors, such as p62 and NBR1, that simultaneously bind both mono- and poly-ubiquitinated substrates act as adaptors between ubiquitination and autophagy. The autophagosome then fuses with and delivers its contents to the lysosome. An in vitro study showed that PM-driven oxidative damage was associated with increases in Atg5, Beclin 1, and light chain 3 protein expressions, suggesting that autophagy plays an important role in regulating particle cytotoxicity.
| Tauopathies in Neurological Disorders|| |
Many neurological disorders are characterized by the deposition of insoluble proteins in cells of the neural system. Clinically, molecular neuropathology has applied a classification system of neurodegenerative diseases based on this protein accumulation. For example, intraneuronal accumulation of tau proteins is considered to be an important hallmark of the development of Alzheimer's disease. Microtubule-associated tau is one protein that has important functions in healthy neurons, but forms insoluble deposits in diseases now known collectively as tauopathies. Overexpression of tau can cause its hyperphosphorylation. In AD brains, hyperphosphorylated levels of tau are around 3–4 times higher than levels in normal adult brains. Tau overexpression in neuroblastoma cells can lead to tau aggregations and the appearance of smaller proteolytic fragments. The degradative mechanisms, such as autophagy, that remove tau from cells are considered to be essential functions for maintaining the brain's health. Autophagosome dysfunction and loss of basal autophagy may lead to neurodegeneration, whereas activation of autophagy can remove aggregated oxidized/diseased proteins. Previous studies showed that autophagy dysfunction was associated with AD. Therefore, dysfunction of removal mechanisms, such as autophagy dysfunction related to tau accumulation in the brain, may be important in explaining the initiation of neurological disorders.
| Conclusions|| |
Epidemiological and toxicological evidence has demonstrated a possible association between neurodegenerative disorders and particulate air pollution. However, the pathophysiology of neurodegenerative disorders such as PD caused by air pollution remains unclear. Aging is an important public health issue worldwide; therefore, attention should be paid to possible risk factors in neurological diseases. Evidence has shown that the elderly may at potential risk of developing air pollution-associated brain dysfunction and damage. It is fundamental and critical to explore causal evidence and pathomechanisms to fill in gaps between current epidemiological and toxicological knowledge regarding air pollution in brain damage. This knowledge should be provided to improve the health of aging subjects.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Brown RC, Lockwood AH, Sonawane BR. Neurodegenerative diseases: An overview of environmental risk factors. Environ Health Perspect 2005;113:1250-6.
Goldman JG, Litvan I. Mild cognitive impairment in Parkinson's disease. Minerva Med 2011;102:441-59.
Janvin CC, Larsen JP, Salmon DP, Galasko D, Hugdahl K, Aarsland D, et al.
Cognitive profiles of individual patients with Parkinson's disease and dementia: Comparison with dementia with lewy bodies and Alzheimer's disease. Mov Disord 2006;21:337-42.
Bläsi S, Zehnder AE, Berres M, Taylor KI, Spiegel R, Monsch AU, et al.
Norms for change in episodic memory as a prerequisite for the diagnosis of mild cognitive impairment (MCI). Neuropsychology 2009;23:189-200.
Brunekreef B, Holgate ST. Air pollution and health. Lancet 2002;360:1233-42.
Pope CA 3rd
, Burnett RT, Thurston GD, Thun MJ, Calle EE, Krewski D, et al.
Cardiovascular mortality and long-term exposure to particulate air pollution: Epidemiological evidence of general pathophysiological pathways of disease. Circulation 2004;109:71-7.
Dominici F, Peng RD, Bell ML, Pham L, McDermott A, Zeger SL, et al.
Fine particulate air pollution and hospital admission for cardiovascular and respiratory diseases. JAMA 2006;295:1127-34.
Olivieri D, Scoditti E. Impact of environmental factors on lung defences. Eur Respir Rev 2005;14:51-6.
Brook RD, Rajagopalan S, Pope CA 3rd
, Brook JR, Bhatnagar A, Diez-Roux AV, et al.
Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation 2010;121:2331-78.
Colais P, Faustini A, Stafoggia M, Berti G, Bisanti L, Cadum E, et al.
Particulate air pollution and hospital admissions for cardiac diseases in potentially sensitive subgroups. Epidemiology 2012;23:473-81.
Künzli N, Jerrett M, Mack WJ, Beckerman B, LaBree L, Gilliland F, et al.
Ambient air pollution and atherosclerosis in los angeles. Environ Health Perspect 2005;113:201-6.
Power, M. C. et al.
Traffic-related air pollution and cognitive function in a cohort of older men. Environ Health Perspect 2011;119:682-687.
Weuve J, Puett RC, Schwartz J, Yanosky JD, Laden F, Grodstein F, et al.
Exposure to particulate air pollution and cognitive decline in older women. Arch Intern Med 2012;172:219-27.
Lim YH, Kim H, Kim JH, Bae S, Park HY, Hong YC, et al.
Air pollution and symptoms of depression in elderly adults. Environ Health Perspect 2012;120:1023-8.
Kioumourtzoglou MA, Power MC, Hart JE, Okereke OI, Coull BA, Laden F, et al.
The association between air pollution and onset of depression among middle-aged and older women. Am J Epidemiol 2017;185:801-9.
Wilker EH, Preis SR, Beiser AS, Wolf PA, Au R, Kloog I, et al.
Long-term exposure to fine particulate matter, residential proximity to major roads and measures of brain structure. Stroke 2015;46:1161-6.
Chen JC, Wang X, Wellenius GA, Serre ML, Driscoll I, Casanova R, et al.
Ambient air pollution and neurotoxicity on brain structure: Evidence from women's health initiative memory study. Ann Neurol 2015;78:466-76.
Casanova R, Wang X, Reyes J, Akita Y, Serre ML, Vizuete W, et al.
A voxel-based morphometry study reveals local brain structural alterations associated with ambient fine particles in older women. Front Hum Neurosci 2016;10:495.
Costa LG, Cole TB, Coburn J, Chang YC, Dao K, Roqué PJ, et al.
Neurotoxicity of traffic-related air pollution. Neurotoxicology 2017;59:133-9.
Gerlofs-Nijland ME, van Berlo D, Cassee FR, Schins RP, Wang K, Campbell A, et al.
Effect of prolonged exposure to diesel engine exhaust on proinflammatory markers in different regions of the rat brain. Part Fibre Toxicol 2010;7:12.
Levesque S, Taetzsch T, Lull ME, Kodavanti U, Stadler K, Wagner A, et al.
Diesel exhaust activates and primes microglia: Air pollution, neuroinflammation, and regulation of dopaminergic neurotoxicity. Environ Health Perspect 2011;119:1149-55.
Campbell A, Oldham M, Becaria A, Bondy SC, Meacher D, Sioutas C, et al.
Particulate matter in polluted air may increase biomarkers of inflammation in mouse brain. Neurotoxicology 2005;26:133-40.
Rosano C, Marsland AL, Gianaros PJ. Maintaining brain health by monitoring inflammatory processes: A mechanism to promote successful aging. Aging Dis 2012;3:16-33.
Guerra R, Vera-Aguilar E, Uribe-Ramirez M, Gookin G, Camacho J, Osornio-Vargas AR, et al.
Exposure to inhaled particulate matter activates early markers of oxidative stress, inflammation and unfolded protein response in rat striatum. Toxicol Lett 2013;222:146-54.
BéruBé K, Aufderheide M, Breheny D, Clothier R, Combes R, Duffin R, et al
. In vitro
models of inhalation toxicity and disease. The report of a FRAME workshop. Altern Lab Anim 2009;37:89-141.
Chen LC, Lippmann M. Effects of metals within ambient air particulate matter (PM) on human health. Inhal Toxicol 2009;21:1-31.
Garcia GJ, Kimbell JS. Deposition of inhaled nanoparticles in the rat nasal passages: Dose to the olfactory region. Inhal Toxicol 2009;21:1165-75.
Suwannasual U, Lucero J, McDonald JD, Lund AK. Exposure to traffic-generated air pollutants mediates alterations in brain microvascular integrity in wildtype mice on a high-fat diet. Environ Res 2018;160:449-61.
Kirkham PA, Barnes PJ. Oxidative stress in COPD. Chest 2013;144:266-73.
Nakahira K, Cloonan SM, Mizumura K, Choi AM, Ryter SW. Autophagy: A crucial moderator of redox balance, inflammation, and apoptosis in lung disease. Antioxid Redox Signal 2014;20:474-94.
Levine B, Mizushima N, Virgin HW. Autophagy in immunity and inflammation. Nature 2011;469:323-35.
Xie Z, Nair U, Klionsky DJ. Atg8 controls phagophore expansion during autophagosome formation. Mol Biol Cell 2s008;19:3290-8.
Mizumura K, Cloonan SM, Haspel JA, Choi AMK. The emerging importance of autophagy in pulmonary diseases. Chest 2012;142:1289-99.
Deng X, Zhang F, Rui W, Long F, Wang L, Feng Z, et al.
PM2.5-induced oxidative stress triggers autophagy in human lung epithelial A549 cells. Toxicol In Vitro
Lai CH, Lee CN, Bai KJ, Yang YL, Chuang KJ, Wu SM, et al.
Protein oxidation and degradation caused by particulate matter. Sci Rep 2016;6:33727.
Kovacs GG. Molecular pathological classification of neurodegenerative diseases: Turning towards precision medicine. Int J Mol Sci 2016;17. pii: E189.
Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med 2011;1:a006189.
Williams DR. Tauopathies: Classification and clinical update on neurodegenerative diseases associated with microtubule-associated protein tau. Intern Med J 2006;36:652-60.
Liazoghli D, Perreault S, Micheva KD, Desjardins M, Leclerc N. Fragmentation of the Golgi apparatus induced by the overexpression of wild-type and mutant human tau forms in neurons. Am J Pathol 2005;166:1499-514.
Iqbal K, Liu F, Gong CX, Grundke-Iqbal I. Tau in Alzheimer disease and related tauopathies. Curr Alzheimer Res 2010;7:656-64.
Chesser AS, Pritchard SM, Johnson GV. Tau clearance mechanisms and their possible role in the pathogenesis of Alzheimer disease. Front Neurol 2013;4:122.
Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell 2008;132:27-42.
Wolfe DM, Lee JH, Kumar A, Lee S, Orenstein SJ, Nixon RA, et al.
Autophagy failure in Alzheimer's disease and the role of defective lysosomal acidification. Eur J Neurosci 2013;37:1949-61.