Current Medicinal Chemistry - Volume 18, Issue 12, 2011

Epigenetics is defined as heritable changes in gene expression which do not alter the DNA sequence. This is achieved through changes to chromatin structure: genes are inactivated when chromatin is condensed and expressed when chromatin is extended. These dynamic chromatin states are controlled by reversible epigenetic patterns of DNA methylation and histone modification. There is now increasing evidence th Read More

In recent years, molecular research has brought to light a series of mechanisms involved in the regulation of gene function without altering the DNA sequence. These mechanisms are described with the term “epigenetics” and include modifications in the structure of the human genome, leading to heritable and potentially reversible changes in gene expression. There is now increasing evidence suggesting that several cha Read More

Fetal growth is a complex process depending on the genetics of the fetus, the availability of nutrients to the fetus, maternal nutrition and various growth factors and hormones of maternal, fetal and placental origin. The IGF system, and more particularly IGF2, is one of the most important endocrine and paracrine growth systems regulating fetal and placental growth (reviewed in [1]). The IGF2 gene is regulated by genomic Read More

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders affecting elderly people (over 65 years old). Only a small percentage (less than 5%) of the disease is consistent with the Mendelian form of inheritance. The rest, named as Late Onset Alzheimer's Disease (more than 95%), is characterized as a complex multi-factorial disorder, missing familial traits. Although some genes have been implicat Read More

Epigenetic modifications, which are heritable changes in gene expression not involving DNA sequence alterations, are important early events in the multi -step process of tumorigenesis. Among them, DNA methylation and histone acetylation are the most extensively studied. Although they are, by definition, somatically heritable, epigenetic modifications of DNA and histones are also reversible. This characteristic difference from Read More

The abuse of substances such as ethanol, cocaine, amphetamines and heroin is associated with toxic effects on almost every system of the organism. Furthermore, the transition from occasional-recreational use to chronic abuse and addiction is a serious psychiatric disorder with only few chances for effective and definitive treatment since most individuals relapse, even after long periods of abstinence. It is therefore of Read More

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), characterized by inflammation, demyelination and axonal loss underlying progressive clinical disability. The chronic inflammatory tissue damage involving myelin and axons is driven by autoreactive T cells and represents a key mechanism in the immunopathogenesis of MS. Over the last few years, evidence from MS and experimental mode Read More

Clinical studies provide overwhelming evidence for the importance of proteolytic imbalance and the upregulation of diverse protease classes in diseases such as cancer and arthritis. While the complex nature of proteolytic networks has hampered the development of protease inhibitors for these indications, aberrant enzyme activity could be successfully exploited for the development of proteasesensitive drug delivery syste Read More

Micro- and macro-vascular complications are the leading causes of morbidity and mortality in type 1 and type 2 diabetic patients. Despite the vast clinical experience linking diabetic metabolic abnormalities to cardiovascular lesions, the molecular basis of individual susceptibility to diabetic cardiovascular injury is still largely unknown. Significant advances in this area may come from studies on suitable animal models. Althou Read More

The neuropeptide substance P (SP) shows a widespread distribution in both the central and peripheral nervous systems and it is known that after binding to the neurokinin-1 (NK-1) receptors, SP regulates many biological functions in the central nervous system such as emotional behaviour, stress, depression, anxiety, emesis, migraine, alcohol addiction and neurodegeneration. SP has been also implicated in pain, inflammati Read More

Aberrant oxidative pathways of catecholamine neurotransmitters, i.e. dopamine and norepinephrine, are an important biochemical correlate of catecholaminergic neuron loss in some disabling neurodegenerative diseases of the elderly, notably Parkinson's disease. In an oxidative stress setting, under conditions of elevated lipid peroxidation, iron accumulation, impaired mitochondrial functioning and antioxidant depletion, Read More

Dietary intakes of tomatoes and tomato products containing lycopene have been shown to be associated with decreased risk of chronic diseases, such as cancer. Although several mechanisms, including modulation of gap junction communication and enhancement of immune system, are thought to be implicated in its beneficial activities, evidence is accumulating to suggest that lycopene may act as a modulator of intracel Read More

Tight junctions (TJs) play pivotal roles in the fence and barrier functions of epithelial and endothelial cell sheets. Since the 1980s, the modulation of the TJ barrier has been utilized as a method for drug absorption. Over the last decade, the structural and functional biochemical components of TJs, such as occludin and claudin, have been determined, providing new insights into TJ-based pharmaceutical therapy. For example, the mo Read More

Autophagy is a self-renewal process in cells by recycling redundant materials through lysosomal machinery. The basal level of autophagy in eukaryotic cells plays a “housekeeping” role by degrading redundant cellular materials and providing nutrients and energy. However acute and sustained autophagy may cause autophagic cell death. These two features of autophagy are consistent with its complex roles in both on Read More

There is an urgent need for the design and development of new and selective drugs for the treatment of malaria and bacterial infections as these pathogens are developing resistance to presently available therapies. Malaria is a life threatening disease in many countries and responsible for almost one million deaths annually. In particular, drug-resistant malarial parasites are hindering effective control of malaria and prompti Read More