Pharmacoepigenetic Processors: Epigenetic Drugs, Drug Resistance, Toxicoepigenetics, and Nutriepigenetics

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

“…The pharmacogenomic machinery is composed by a network of gene clusters coding for proteins and enzymes responsible for drug targeting and processing as well as critical components of the epigenetic machinery that regulate gene expression [60,61]. The pharmagenes involved in the pharmacogenomic response to drugs can be classified into five major categories: (i) Pathogenic genes (Table 1) which are associated with disease pathogenesis [62]; (ii) mechanistic genes coding for components of enzymes, receptor subunits, transmitters, and messengers associated with the mechanism of action of drugs; (iii) metabolic genes of different categories that encode phase I-II reaction enzymes responsible for drug metabolism. Phase-I reaction enzymes include (in alphabetical order) alcohol dehydrogenases, aldehyde dehydrogenases, aldo-keto reductases, amine oxidases, carbonyl reductases, cytidine deaminases, cytochrome P450 family (CYPs) of mono-oxygenases, cytochrome b5 reductase, dihydropyrimidine dehydrogenase, esterases, epoxidases, flavin-containing monooxygenases, glutathione reductase/peroxidases, peptidases, prostaglandin endoperoxide synthases, short-chain dehydrogenases, reductases, superoxide dismutases, and xanthine dehydrogenase.…”

Stability and anti-proliferative properties of biologically active compounds extracted from Cistus L. after sterilization treatments

“…Because glioblastoma tumors are chemotherapy-resistant with limited treatment options, investigation on new combination therapies or cancer immunotherapy has been prioritized by several research groups [47][48][49] . Recent evidence from numerous laboratories suggests that phytochemicals affect the immune response [50][51][52][53] . Gao et al 54 reported the effects of polyphenols on the development of several lymphocytic responses in vitro.…”

“…Furthermore, Chen and co-workers 51 proposed that inhibition of indoleamine 3,5-dioxygenase-1 (IDO-1) protein, produced by cancer, may be an important mechanism of polyphenols in chemoprevention or combinatorial cancer therapy. Indeed, it has been reported that biologically active compounds exhibit potent enzyme inhibitory activity in IDO-1, which in turn may ameliorate cancer immunosuppressive environment and attenuate metastatic potential 52,55 .…”

How plausible is an Alzheimer’s disease vaccine?

“…Methodologically, a vaccine against AD is technically feasible; however, important procedural aspects should be changed for a tentative clinical success, including (i) the development of multitarget AD immunotherapies: addressing the binomial APP-MAPT target is insufficient to halt disease progression from early (asymptomatic) stages of AD; it is essential to address other targets (i.e. APOE, TOMM40, and other pathogenic gene products) which interact with APP processing to generate amyloid deposits and neurodegeneration; (ii) the optimization of antibody titers and epitopes by improving immunization procedures and vaccinomics; (iii) the pharmacogenetic/pharmacoepigenetic validation of the immunization procedure: only 20% of AD patients are extensive metabolizers for conventional treatments; immunization is not an exception and pharmaco(Epi)genetic geno-phenotyping should be a preceptive test for personalized interventions; vaccines might become, with time, a novel modality of epigenetic intervention to reversibly regulate gene expression in complex disorders such as AD; (iv) the prophylactic treatment of genetically stratified patients at a pre-symptomatic stage: the genomic background of each patient modulates disease progression and may elicit a differential immunotherapeutic response to AD vaccines (either passive or active procedures); and (v) the definition of primary endpoints in prevention, based on objective/multifactorial biomarkers (other than Aβ, Tau, and conventional psychometrics), for an efficient assessment of vaccine efficacy and safety: novel biomarkers should include genomic, epigenetic, and proteomic signatures in body fluids or functional neuroimaging; especially important are epigenetic and proteomic markers which are modifiable with disease progression and sensitive to therapeutic intervention in presymptomatic stages [13,21]. Even with exquisite protocols, a successful vaccine would be potentially useful in at most 20-30% of the defined cases, according to the genetic, epigenetic, and pharmacogenetic background of AD patients [13].…”

“…Other more relevant genomic defects (Mendelian mutations, susceptibility SNPs, and CNV) and epigenetic aberrations (DNA methylation, chromatin/histone modifications, and microRNA dysregulation), responsible for the abnormal expression of specific genes and anomalies in protein conformation, are pathogenic events that cannot be neglected in AD therapeutics (primary and secondary prevention) [13,14]. A typical paradigm is apolipoprotein E (ApoE).…”