After long incubational time, slightly over-expressed alphasynuclein can accumulate enough in the neurons to cause PD, while in the glial cells, efficient protein degradation system or the cell division might help them to prevent the accumulation. Global CpG methylation decreases with age, and specific genes, such as cancer suppressors, are down-regulated by decreased promoter region CpG island methylation. Our findings suggest that in PD patients, normally occurring SNCA CpG-2 hypermethylation does not occur, causing over-expression of alpha-synuclein and leading to its accumulation which, in turn, causes PD. Organisms respond to xenobiotics -natural compounds or artificial substances not normally present in the body such as drugs, antibiotics, pollutants and carcinogens by deactivating and excreting those products via a series of enzymes located mostly in the liver and, to a lesser extent, in the small intestine. Three sets of enzymes contribute to the process. First, Phase I enzymes chemically modify the xenobiotics by multiple mechanisms. Phase II components then conjugate the products with glucuronic acid, sulphuric acid or glutathione, to make them more soluble. Finally, transporter members of the Phase III help to excrete the modified components via urine or bile. Phase I of the pathway is Tripdiolide carried out by members of the cytochrome P450 superfamily, a large and diverse group of hemoproteins present in most organisms and whose activity is responsible for almost 75% of the total drug metabolism in higher eukaryotes. Phase II involves the conjugation of modified xenobiotics by transferases like glutathione s-transferases and UDP-glucuronosyl transferases, which normally results in less active metabolites that are also more soluble in water. Drug transporters such as the ATP-binding-cassette superfamily comprise Phase III of the detoxification pathway. They eliminate and distribute the less active, more soluble products from Phase II metabolism. The synthesis of several Cyp enzymes is induced in response to specific drugs or naturally occurring molecules. In some cases the enzyme activity is also modified by interaction with the drug. As changes in Cyp activity will affect the metabolism and elimination of various drugs, understanding and identifying genetic factors that can modify the Tenuifoliside-C detoxification response is especially important when using drugs with noticeable side-effects, with small therapeutic windows or necessary to treat critically ill patients. The product of the retinoblastoma gene and its two related proteins, p107 and p130, control the transition between G1 and S phase, thus preventing abnormal cell proliferation. They function by interacting with the E2F family of transcription factors, which in turn regulate multiple genes essential to progress through the G1-S phase. Two groups of factors can be identified within the mammalian E2F family, according to their biochemical properties, effects of target genes, and expression through the cell cycle: E2F1-2-3 in one hand and E2F4 through E2F8 on the other encoded by Simian Virus 40 has been shown to bind and inactivate members of the pRb pathway, resulting in upregulation of E2F proteins and E2F activity, with the subsequent induction of cellular proliferation and tumorigenesis in different systems, both in vivo and in vitro. TAg binds the pRb proteins through its LXCXE peptide motif, and mutations in TAg altering or eliminating the LXCXE domain fail to interact with the pRb proteins and to induce cell proliferation. In addition to its role inducing cell proliferation and tumorigenesis, we have previously shown that, when expressed ectopically in intestinal enterocytes, TAg also downregulates the endogenous and constitutive RNA levels of multiple detoxification components from Phases I, II and III. This effect requires an intact LXCXE motif in TAg, suggesting that perhaps the transcription of detoxification components normally requires pRb proteins.