While environmental factors are largely implicated in the etiology of neurodegenera tive disease, at present the various sources respon sible for the chronic neuroinflammation leading to central nervous system pathology are poorly understood. Air pollution is a mixture comprised of several com ponents, including particulate matter, kinase inhibitor MEK162 gases, and metals, such as vanadium, nickel, and manganese. This toxin is readily available in the environment in many forms from multiple sources and exposure occurs across and individuals entire lifetime. In fact, in the US alone, millions of people are exposed to levels of air pollution above established safety standards. This is of sig nificant concern, as diverse forms of air pollution have been widely implicated in inflammation and oxidative stress in humans.

While the majority of studies focus on the effects of air pollution in cardiovascular and Inhibitors,Modulators,Libraries pulmonary disease, accumulating evidence now points to a new role for air pollution in CNS disease. For example, human studies have shown that living Inhibitors,Modulators,Libraries in conditions with elevated air pollution is associated with decreased cogni tive function, AD PD like neuropathology, and increased stroke incidence. Even the individual air pollution components such as manganese have been linked to CNS pathology, as elevated levels of manga nese in the Inhibitors,Modulators,Libraries air are linked to enhanced PD risk. Consistent with human reports, recent animal studies reveal that exposure to diverse forms of air pollution by inhalation, such as urban PM, ozone, DE, and manganese results in a common pro inflam matory response and oxidative stress in the brain.

How ever, given the significant Inhibitors,Modulators,Libraries expense of inhalation exposure studies, the majority of this experimental work is based on short term studies, with only high exposure levels tested. While these stu dies are critical for understanding how air pollution affects the brain, human exposures Inhibitors,Modulators,Libraries to air pollution typi cally occur at lower concentrations. More specifically, PM levels in polluted US cities peak around 50 ug PM m3, near road PM concentrations http://www.selleckchem.com/products/wortmannin.html are measured around approximately 100 ug PM m3, and occupational exposure to PM occurs around 1000 2000 ug PM m3, where human exposure continues for years. Diesel exhaust is a form of air pollution that has received significant attention regarding its potential effect on human health in both ambient and occupa tional exposure conditions, and several studies have documented the CNS effects of DE. For example, acute, high level DE exposure affects electroencephalogram parameters in adult human subjects. Animal research has shown that the prenatal period is a critical period of vulnerability, where maternal DE exposure affects dopamine neurochemistry and causes motor defi cits in offspring.