Open Access
Epigenetic drug discovery for alzheimer's disease
(Academic Press, 2018) Cacabelos, Ramón; Teijido Hermida, Óscar; Ciencias de la Salud; Osasun Zientziak
Alzheimer's disease (AD) is the most important neurodegenerative disorder in Western countries. Pathological phenotypes of neurodegeneration result from a combination of genomic, epigenomic, metabolic, and environmental factors, which hinders their treatment. Current FDA-approved conventional drugs are purely symptomatic but incapable to halt or, at least, delay the progression of the disease. The epigenetic approach allows the identification of key pathological targets in complex disorders that cannot be explained by conventional genetics. Many of these epigenetic targets may be detected in early asymptomatic stages of the disease. Furthermore, the reversibility and potential restoring of epigenetic aberrations, unlike genetic mutations, sited epigenetic-based therapy as a promising tool to treat those complex disorders. This chapter reviews the main potential epigenetic-based compounds that have been used for preclinical studies during the last decade and those currently submitted to clinical trials for the treatment of AD.
Open Access
Epigenetic mechanisms in the regulation of drug metabolism and transport
(Academic Press, 2019) Teijido Hermida, Óscar; Ciencias de la Salud; Osasun Zientziak
Open Access
Epigenetics of brain aging
(Academic Press, 2018) Cacabelos, Ramón; Teijido Hermida, Óscar; Ciencias de la Salud; Osasun Zientziak
The complexity of human aging and longevity results from a combination of genetic, epigenetic, and environmental factors. Epigenetic mechanisms, including DNA methylation, chromatin structure, and RNA interference, regulate gene expression and control the main metabolic pathways throughout life. This strict epigenetic management becomes progressively defective with age, which increases the risk for the onset of age-related pathologies. This chapter reviews the main alterations of the epigenetic machinery throughout life, with special focus on those affecting the aging brain, as well as the epigenetic control of life span by regulating telomere length and mitochondrial function, with special emphasis on the epigenetic interplay between nuclear and mitochondrial DNA. The last section summarizes the main epigenetic aberrations involving the most prevalent form of pathologic brain deterioration in elderly individuals, Alzheimer's disease, and novel potential epigenetic-based treatments.
Open Access
Pharmacogenomics and epigenomics of age-related neurodegenerative disorders: strategies for drug development
(Royal Society of Chemistry, 2017) Cacabelos, Ramón; Carril, Juan Carlos; Teijido Hermida, Óscar; Ciencias de la Salud; Osasun Zientziak
Open Access
Basic and clinical studies with marine lipofishins and vegetal favalins in neurodegeneration in age-related disorders
(Elsevier, 2018) Cacabelos, Ramón; Lombardi, Valter; Fernández-Novoa, Lucía; Carrera, Iván; Cacabelos, Pablo; Corzo, Lola; Carril, Juan Carlos; Teijido Hermida, Óscar; Ciencias de la Salud; Osasun Zientziak
Over the past 30 years, many different types of nutraceuticals have been produced for the natural management of diverse health conditions. Nutraceuticals are vegetal, marine, or animal bioderivatives in nature. A novel category of nutraceutical compounds is represented by the ProteoLipins, a series of complex lipoproteins derived from natural sources. Among ProteoLipins, LipoFishins (LFs) are a new class of lipoproteins obtained from the muscle of different fish species. Examples of LFs obtained from biomarine sources by means of nondenaturing biotechnological procedures include the following: E-JUR-94013 (DefenVid®), E-CAB-94011 (CabyMar®), E-Congerine-10423 (AntiGan®), E-SAR-94010 (LipoEsar®), and E-MHK-0103 (MineraXin®). Specifically, these compounds show immune-enhancing, cell growth and maturation, antitumoral, hypolipemic, and hormone-modulating properties, respectively. Favalins are a novel category of nutraceuticals extracted from the structural components of the Vicia faba plant. E-PodoFavalin-15999 is a powerful antiparkinsonian agent with procatecholaminergic properties and neuroprotective activity on dopaminergic neurons. Clinical studies with some of these products in different clinical conditions (cardiovascular disorders, dyslipidemia, cancer, Alzheimer's disease, Parkinson's disease, menopause) have revealed that most of the effects of these novel bioproducts are genotype-dependent, showing specific nutrigenomic and pharmacogenomic profiles.