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      Air Pollution–Related Neurotoxicity Across the Life Span

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      Annual Review of Pharmacology and Toxicology
      Annual Reviews

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          Abstract

          Air pollution is a complex mixture of gases and particulate matter, with adsorbed organic and inorganic contaminants, to which exposure is lifelong. Epidemiological studies increasingly associate air pollution with multiple neurodevelopmental disorders and neurodegenerative diseases, findings supported by experimental animal models. This breadth of neurotoxicity across these central nervous system diseases and disorders likely reflects shared vulnerability of their inflammatory and oxidative stress–based mechanisms and a corresponding ability to produce brain metal dyshomeo-stasis. Future research to define the responsible contaminants of air pollution underlying this neurotoxicity is critical to understanding mechanisms of these diseases and disorders and protecting public health.

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          Staging of brain pathology related to sporadic Parkinson’s disease

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            How neuroinflammation contributes to neurodegeneration.

            Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal lobar dementia are among the most pressing problems of developed societies with aging populations. Neurons carry out essential functions such as signal transmission and network integration in the central nervous system and are the main targets of neurodegenerative disease. In this Review, I address how the neuron's environment also contributes to neurodegeneration. Maintaining an optimal milieu for neuronal function rests with supportive cells termed glia and the blood-brain barrier. Accumulating evidence suggests that neurodegeneration occurs in part because the environment is affected during disease in a cascade of processes collectively termed neuroinflammation. These observations indicate that therapies targeting glial cells might provide benefit for those afflicted by neurodegenerative disorders.
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              Parkinson's disease: a dual‐hit hypothesis

              Accumulating evidence suggests that sporadic Parkinson's disease has a long prodromal period during which several non‐motor features develop, in particular, impairment of olfaction, vagal dysfunction and sleep disorder. Early sites of Lewy pathology are the olfactory bulb and enteric plexus of the stomach. We propose that a neurotropic pathogen, probably viral, enters the brain via two routes: (i) nasal, with anterograde progression into the temporal lobe; and (ii) gastric, secondary to swallowing of nasal secretions in saliva. These secretions might contain a neurotropic pathogen that, after penetration of the epithelial lining, could enter axons of the Meissner's plexus and, via transsynaptic transmission, reach the preganglionic parasympathetic motor neurones of the vagus nerve. This would allow retrograde transport into the medulla and, from here, into the pons and midbrain until the substantia nigra is reached and typical aspects of disease commence. Evidence for this theory from the perspective of olfactory and autonomic dysfunction is reviewed, and the possible routes of pathogenic invasion are considered. It is concluded that the most parsimonious explanation for the initial events of sporadic Parkinson's disease is pathogenic access to the brain through the stomach and nose – hence the term ‘dual‐hit’.
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                Author and article information

                Journal
                Annual Review of Pharmacology and Toxicology
                Annu. Rev. Pharmacol. Toxicol.
                Annual Reviews
                0362-1642
                1545-4304
                January 20 2023
                January 20 2023
                : 63
                : 1
                : 143-163
                Affiliations
                [1 ]Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, New York, USA;
                Article
                10.1146/annurev-pharmtox-051921-020812
                36028225
                c6678b8d-7811-47d0-905d-337d49a86ab6
                © 2023

                http://creativecommons.org/licenses/by/4.0/

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