, 2005). Proteasome inhibition has also been shown in neuroblastoma cells exposed to rotenone, ziram, diethyldithiocarbamate, endosulfan, benomyl, and dieldrin (Chou et al., 2008 and Wang et al., 2006). Paraquat has also been noted to impair UPS given by decreased proteasome activity and increased ubiquitinated proteins in DJ-1 deficient mice and dopaminergic neurons (Yang and Tiffany-Castiglioni, 2007 and Yang et al., 2007). Increased degradation of proteasome components has been presented as the mechanism of proteasome inhibition by rotenone, an inducer of Parkinson (Chou et al., 2010). The lysosomal degradation pathway of autophagy is Afatinib purchase known as a self-digestion
process by which cells not only get rid of misfolded proteins, damaged organelles and infectious microorganisms but also provide nutrients during fasting. Defect of this process has found an emerging role
in many human diseases such as cancer, neurodegeneration, diabetes, aging, and disorders of the liver, muscle, and heart (Gonzalez et al., 2011, Levine and Kroemer, 2008 and Shintani and Klionsky, 2004). There are a few reports on the involvement of defective see more autophagy in toxic effects of pesticides. A relationship between autophagy and paraquat-induced apoptosis in neuroblastoma cells was shown by Gonzalez-Polo and colleagues in 2007 (Gonzalez-Polo et al., 2007). This effect was confirmed in another study in which paraquat-induced autophagy was attributed to the occurrence of ER stress (Niso-Santano Cediranib (AZD2171) et al., 2011). Lindan, a broad-spectrum organochlorine pesticide, has been reported to promote
its toxicity through disruption of an autophagic process in primary rat hepatocytes (Zucchini-Pascal et al., 2009) (Fig. 3). Taken together, chronic diseases discussed above are considered as the major disorders affecting public health in the 21st century. The relationship between these diseases and environmental exposures, particularly pesticides increasingly continues to strengthen. Near to all studies carried out in the area of pesticides, and chronic diseases are categorized in the field of epidemiologic evidence or experimental investigation with mechanistic insight into the disease process. Some epidemiologic studies have been debated on their uncertainty in elicitation of a definite conclusion because of some restrictions. However, existence of more than a few dozen reports on the association of one case like brain cancer with exposure to pesticide is enough to create concern even without finding a direct link. Abundance of evidence in this regard has promoted scientist to evaluate the mechanisms by which pesticides develop chronic diseases. Although there remains a lot to do in this way, several mechanisms and pathways have been clarified for pesticide-induced chronic diseases.