Predisposition to Alzheimer's and Age-Related Brain Pathologies by PM2.5 Exposure: Perspective on the Roles of Oxidative Stress and TRPM2 Channel.

Lu Wang,Yanyan Feng,Chaokun Li,Yaling Yin,Dongliang Li,Weidong Wu,Philippa Malko,Lin-Hua Jiang,Sharifah A Syed Mortadza,Lin Yu Wei,Ran Ding

doi:10.3389/fphys.2020.00155

Abstract

Accumulating epidemiological evidence supports that chronic exposure to ambient fine particular matters of <2.5 μm (PM2.5) predisposes both children and adults to Alzheimer’s disease (AD) and age-related brain damage leading to dementia. There is also experimental evidence to show that PM2.5 exposure results in early onset of AD-related pathologies in transgenic AD mice and development of AD-related and age-related brain pathologies in healthy rodents. Studies have also documented that PM2.5 exposure causes AD-linked molecular and cellular alterations, such as mitochondrial dysfunction, synaptic deficits, impaired neurite growth, neuronal cell death, glial cell activation, neuroinflammation, and neurovascular dysfunction, in addition to elevated levels of amyloid β (Aβ) and tau phosphorylation. Oxidative stress and the oxidative stress-sensitive TRPM2 channel play important roles in mediating multiple molecular and cellular alterations that underpin AD-related cognitive dysfunction. Documented evidence suggests critical engagement of oxidative stress and TRPM2 channel activation in various PM2.5-induced cellular effects. Here we discuss recent studies that favor causative relationships of PM2.5 exposure to increased AD prevalence and AD- and age-related pathologies, and raise the perspective on the roles of oxidative stress and the TRPM2 channel in mediating PM2.5-induced predisposition to AD and age-related brain damage.

Highlights

Air pollution has increasingly become an environmental risk to public health worldwide, to people living in large cities
PM2.5, Oxidative Stress and transient receptor potential melastatin 2 (TRPM2) to show that exposure to polluted ambient air is injurious to the brain (Brockmeyer and D’Angiulli, 2016; Clifford et al, 2016; Power et al, 2016; Babadjouni et al, 2017; Cohen et al, 2017; Sripada, 2017; Underwood, 2017; Bencsik et al, 2018)
A recent study introducing TRPM2-KO in the amyloid precursor protein (APP)/presenilin 1 (PS1) mice has disclosed a key role of the TRPM2 channel in amyloid β (Aβ)-induced synaptic deficits, microglial cell activation, and age-related impairment in learning and memory (Ostapchenko et al, 2015)

Summary

Introduction

Air pollution has increasingly become an environmental risk to public health worldwide, to people living in large cities. Subsequent studies by the same group have documented numerous early pathological indicators of neurodegenerative diseases, including accumulation of Aβ42, oxidative stress, neuroinflammation, and neurovascular damage in the brains of children and young people in Mexico City experiencing chronic exposure to high levels of air pollution and PM2.5 (Calderon-Garciduenas et al, 2004, 2008, 2012, 2016, 2018; Gonzalez-Maciel et al, 2017).

Results

Conclusion