Therapeutic Options in Alzheimer's Disease: From Classic Acetylcholinesterase Inhibitors to Multi-Target Drugs with Pleiotropic Activity.

Alzheimer's disease (AD) is a complex/multifactorial brain disorder involving hundreds of defective genes, epigenetic aberrations, cerebrovascular alterations, and environmental risk factors. The onset of the neurodegenerative process is triggered decades before the first symptoms appear, probably due to a combination of genomic and epigenetic phenomena. Therefore, the primary objective of any effective treatment is to intercept the disease process in its presymptomatic phases.

Neuroprotective Effect of Nosustrophine in a 3xTg Mouse Model of Alzheimer's Disease.

Neurodegeneration, characterized by the progressive deterioration of neurons and glial cells, is a feature of Alzheimer's disease (AD). The present study aims to demonstrate that the onset and early progression of neurodegenerative processes in transgenic mice models of AD can be delayed by a cocktail of neurotrophic factors and derived peptides named Nosustrophine, a nootropic supplement made by a peptide complex extracted from the young porcine brain, ensuring neuroprotection and improving neuro-functional recovery. Experimental 3xTg-APP/Bin1/COPS5 transgenic mice models of AD were treated with Nosustrophine at two different early ages, and their neuropathological hallmark and behavior response were analyzed.

Proteomic and Global DNA Methylation Modulation in Lipid Metabolism Disorders with a Marine-Derived Bioproduct.

Dyslipidemia is a significant risk factor for cardiovascular disease and stroke. Our recent findings showed that RCI-1502, a bioproduct derived from the muscle of the European S. pilchardus, has lipid-lowering effects in the liver and heart in high-fat diet (HFD) fed mice.

Natural Bioactive Products as Epigenetic Modulators for Treating Neurodegenerative Disorders.

Neurodegenerative disorders (NDDs) are major health issues in Western countries. Despite significant efforts, no effective therapeutics for NDDs exist. Several drugs that target epigenetic mechanisms (epidrugs) have been recently developed for the treatment of NDDs, and several of these are currently being tested in clinical trials.

Cardiovascular and lipid-lowering effects of a marine lipoprotein extract in a high-fat diet-induced obesity mouse model.

Obesity is a major health challenge worldwide, with implications for diabetes, hypertension and cardiovascular disease (CVD). Regular consumption of dark-meat fish is linked to a lower incidence of CVD and associated metabolic disorders due to the presence of long-chain omega-3 fatty acid ethyl esters in fish oils. The aim of the present study was to determine whether a marine compound like a sardine lipoprotein extract (RCI-1502), regulates fat accumulation in the heart of a high-fat diet-induced (HFD) mouse model of obesity.

DNA Methylation as a Biomarker for Monitoring Disease Outcome in Patients with Hypovitaminosis and Neurological Disorders.

DNA methylation remains an under-recognized diagnostic biomarker for several diseases, including neurodegenerative disorders. In this study, we examined differences in global DNA methylation (5mC) levels in serum samples from patients during the initial- and the follow-up visits. Each patient underwent a blood analysis and neuropsychological assessments.

Pharmacogenetics of anxiety and depression in Alzheimer's disease.

Anxiety and depression coexist with cognitive impairment in Alzheimer's disease along with other concomitant disorders (>60%), which require multipurpose treatments. Polypharmaceutical regimens cause drug-drug interactions and adverse drug reactions, potentially avoidable in number and severity with the implementation of pharmacogenetic procedures. The accumulation of defective variants (>30 genes per patient in more than 50% of cases) in pharmagenes (pathogenic, mechanistic, metabolic, transporter, pleiotropic) influences the therapeutic response to antidementia, antidepressant and anxiolytic drugs in polyvalent regimens.

Nosustrophine: An Epinutraceutical Bioproduct with Effects on DNA Methylation, Histone Acetylation and Sirtuin Expression in Alzheimer's Disease.

Alzheimer's disease (AD), the most common cause of dementia, causes irreversible memory loss and cognitive deficits. Current AD drugs do not significantly improve cognitive function or cure the disease. Novel bioproducts are promising options for treating a variety of diseases, including neurodegenerative disorders.

Pharmacogenomics of Alzheimer's Disease: Novel Strategies for Drug Utilization and Development.

Alzheimer's disease (AD) is a priority health problem in developed countries with a high cost to society. Approximately 20% of direct costs are associated with pharmacological treatment. Over 90% of patients require multifactorial treatments, with risk of adverse drug reactions (ADRs) and drug-drug interactions (DDIs) for the treatment of concomitant diseases such as hypertension (>25%), obesity (>70%), diabetes mellitus type 2 (>25%), hypercholesterolemia (40%), hypertriglyceridemia (20%), metabolic syndrome (20%), hepatobiliary disorder (15%), endocrine/metabolic disorders (>20%), cardiovascular disorder (40%), cerebrovascular disorder (60-90%), neuropsychiatric disorders (60-90%), and cancer (10%).

Personalized Management and Treatment of Alzheimer's Disease.

Alzheimer’s disease (AD) is a priority health problem with a high cost to society and a large consumption of medical and social resources. The management of AD patients is complex and multidisciplinary. Over 90% of patients suffer from concomitant diseases and require personalized therapeutic regimens to reduce adverse drug reactions (ADRs), drug−drug interactions (DDIs), and unnecessary costs.

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions.

Adverse drug reactions (ADRs) rank as one of the top 10 leading causes of death and illness in developed countries. ADRs show differential features depending upon genotype, age, sex, race, pathology, drug category, route of administration, and drug-drug interactions. Pharmacogenomics (PGx) provides the physician effective clues for optimizing drug efficacy and safety in major problems of health such as cardiovascular disease and associated disorders, cancer and brain disorders.

Atremorine in Parkinson's disease: From dopaminergic neuroprotection to pharmacogenomics.

Atremorine is a novel bioproduct obtained by nondenaturing biotechnological processes from a genetic species of Vicia faba. Atremorine is a potent dopamine (DA) enhancer with powerful effects on the neuronal dopaminergic system, acting as a neuroprotective agent in Parkinson's disease (PD). Over 97% of PD patients respond to a single dose of Atremorine (5 g, p.

Influence of Pathogenic and Metabolic Genes on the Pharmacogenetics of Mood Disorders in Alzheimer's Disease.

Background: Mood disorders represent a risk factor for dementia and are present in over 60% of cases with Alzheimer's disease (AD). More than 80% variability in drug pharmacokinetics and pharmacodynamics is associated with pharmacogenetics.

Methods: Anxiety and depression symptoms were assessed in 1006 patients with dementia (591 females, 415 males) and the influence of pathogenic (APOE) and metabolic (CYP2D6, CYP2C19, and CYP2C9) gene variants on the therapeutic outcome were analyzed after treatment with a multifactorial regime in a natural setting.

Nutrition, Health, and Disease: Role of Selected Marine and Vegetal Nutraceuticals.

The investigation of new alternatives for disease prevention through the application of findings from dietary and food biotechnology is an ongoing challenge for the scientific community. New nutritional trends and the need to meet social and health demands have inspired the concept of functional foods and nutraceuticals which, in addition to their overall nutritional value, present certain properties for the maintenance of health. However, these effects are not universal.

Pharmacogenetics of Atremorine-Induced Neuroprotection and Dopamine Response in Parkinson's Disease.

Atremorine is a novel bioproduct with neuroprotective effects on dopaminergic neurons and a natural L-DOPA donor in Parkinson's disease (PD). In the present study, we show the effects of a single dose of Atremorine (5 g, p. o.

Sirtuins in Alzheimer's Disease: SIRT2-Related GenoPhenotypes and Implications for PharmacoEpiGenetics.

Sirtuins (SIRT1-7) are NAD⁺-dependent protein deacetylases/ADP ribosyltransferases with important roles in chromatin silencing, cell cycle regulation, cellular differentiation, cellular stress response, metabolism and aging. Sirtuins are components of the epigenetic machinery, which is disturbed in Alzheimer's disease (AD), contributing to AD pathogenesis. There is an association between the genotype (rs10410544) (50.

Role of bioactive lipofishins in prevention of inflammation and colon cancer.

Many clinical conditions exist in which it is desirable to stimulate or suppress the immune system, and many different drugs are able to do this. It is also well known that nutrition may affect human health and immune responses. Nutritional factors are crucial components of the diet and essential for normal growth and development of both vertebrate and invertebrate organisms.

E-MHK-0103 (Mineraxin™): A Novel Nutraceutical with Biological Properties in Menopausal Conditions.

Background: Menopause-derived estrogen deprivation and related endocrine factors are linked to some symptoms typical of middle-aged women, such as hot flashes, aches, joint pain, stiffness, depressed mood, bone degeneration, nutritional dysfunction, or difficulty to maintain body mass. Clinical approaches to these problems often involve hormone replacement therapy and other modalities of therapeutic intervention. However, the well-known side effects associated with other pharmacological alternatives have led physicians and patients to pursue new strategies to alleviate these symptoms.

Novel Therapeutic Strategies for Dementia.

Dementia represents a major problem of health and disability, with a relevant economic impact on our society. Despite important advances in pathogenesis, diagnosis and treatment, its primary causes still remain elusive, accurate biomarkers are not well characterized, and the available pharmacological treatments are not cost-effective. Alzheimer disease (AD), the most prevalent form of dementia, is a polygenic/multifactorial/complex disorder in which hundreds of defective genes distributed across the human genome may contribute to its pathogenesis.

Genomics of Dementia: APOE- and CYP2D6-Related Pharmacogenetics.

Dementia is a major problem of health in developed societies. Alzheimer's disease (AD), vascular dementia, and mixed dementia account for over 90% of the most prevalent forms of dementia. Both genetic and environmental factors are determinant for the phenotypic expression of dementia.

Genomics and pharmacogenomics of brain disorders.

CNS disorders are the third major problem of health in developed countries, with approximately 10% of direct costs associated with a pharmacological treatment of doubtful cost-effectiveness. There is an alarming abuse of psychotropic drugs worldwide and only 20-30% of patients with CNS disorders appropriately respond to conventional drugs. The pathogenesis of most CNS disorders is the result of the interplay of genetic and epigenetic factors with environmental factors leading to post-transcriptional changes and proteomic and metabolomic dysfunctions.

Decreased levels of serum nitric oxide in different forms of dementia.

Nitric oxide is involved in normal physiological functions and also in pathological processes leading to tissue damage due, in part, to its free radical nature (oxidative stress). Oxidative stress and vascular dysfunction have been recognized as contributing factors in the pathogenesis of Alzheimer disease (AD) and vascular dementia (VD). In order to study the possible links between these processes and dementia, we have analysed plasma amyloid-beta(1-42) levels (Abeta) and total nitric oxide (NOx), apolipoprotein E (ApoE), lipids, vitamin B12, and folate concentrations in the serum of 99 patients with dementia and 55 age-matched non-demented controls.

Phenotypic profiles and functional genomics in Alzheimer's disease and in dementia with a vascular component.

Alzheimer's disease (AD) and dementia with vascular component (DVC) are the most prevalent forms of dementia. Both clinical entities share many similarities, but they differ in major phenotypic and genotypic profiles as revealed by structural and functional genomics studies. Comparative phenotypic studies have identified significant differences in 25% of more than 100 parametric variables, including anthropometry, cardiovascular function, aortic atherosclerosis, brain atrophy, blood pressure, blood biochemistry, hematology, thyroid function, folate and vitamin B12 levels, brain hemodynamics and lymphocyte markers.

Cerebrovascular risk factors in Alzheimer's disease: brain hemodynamics and pharmacogenomic implications.

Recent evidence indicates that different vascular risk factors are present in Alzheimer's disease (AD) and other prevalent dementia types probably contributing to deterioration of cerebrovascular function, thus enhancing neurodegeneration and premature neuronal death due to a reduction in brain perfusion. Brain blood flow shows a reduced velocity and increased pulsatility (PI) and resistance indices (RI) in different types of dementia and in diabetes and hypertension, as well. High levels of diastolic blood pressure correlate with diminished brain blood flow and elevated PI and RI, accompanied by cognitive deterioration.

Positive effects of cerebrolysin on electroencephalogram slowing, cognition and clinical outcome in patients with postacute traumatic brain injury: an exploratory study.

The potential effects of Cerebrolysin (EBEWE Pharma, Unterach, Austria), a peptide preparation with neurotrophic activity, on brain bioelectrical activity, cognitive performance and clinical outcome in postacute traumatic brain injury (TBI) patients, were investigated in an exploratory study. A decrease in slow electroencephalogram (EEG) activity and an increase in fast frequencies were observed after the administration of Cerebrolysin. This EEG-activating effect was not influenced by TBI time course or severity, nor by the chronic treatment with nootropic compounds.