Current Drug Targets - Volume 11, Issue 10, 2010

Over the past decades, metabolic dysfunction has emerged as one of the most common pathological condition underlying the neurodegenerative process in distinct disorders of the central and peripheral nervous system. Due to improvements in life expectancy, the world's population is ageing rapidly and the incidence of neurodegenerative diseases linked to protein misfolding and aggregation has increased and will dramaticall Read More

Alzheimer's disease (AD) is the most common form of dementia in old age. Cognitive impairment in AD may be partially due to overall hypometabolism. Indeed, AD is characterized by an early region-specific decline in glucose utilization and by mitochondrial dysfunction, which have deleterious consequences for neurons through increased production of reactive oxygen species (ROS), ATP depletion and activation of c Read More

Prion diseases are fatal neurodegenerative disorders that affect humans and other mammals. The hallmark of these diseases is the conformational change of the cellular prion protein (PrPC) to the misfolded protein capable of propagation and associated with neurodegeneration, named prion (PrPSc). In a strict sense, prion diseases are a consequence of aberrations in the metabolism of the cellular prion protein (PrPC). This bri Read More

Huntington's disease (HD) is a genetic neurodegenerative disease selectively leading to striatal neurodegeneration, but also affecting the cortex and the hypothalamus. Although it is hard to predict the sequence of celldamaging events occurring in HD patients, several pathological mechanisms have been proposed to explain HD selective neurodegeneration and disease symptomatology. Abnormalities in mitochondri Read More

Huntington's disease (HD) is neither a fatal hereditary neurodegenerative disorder without satisfactory treatments nor a cure. It is caused by a CAG repeat expansion in the huntingtin gene. The clinical symptoms involve motor-, cognitive- and psychiatric disturbances. Recent studies have shown that non-motor symptoms and signs, such as mood changes, sleep disturbances and metabolic alterations often occur before the onset Read More

Lower motor neuron (LMN) degeneration occurs in several diseases that affect patients from neonates to elderly and can either be genetically transmitted or occur sporadically. Among diseases involving LMN degeneration, spinal muscular atrophy (SMA) and spinal bulbar muscular atrophy (Kennedy's disease, SBMA) are pure genetic diseases linked to loss of the SMN gene (SMA) or expansion of a polyglutamine tract in the a Read More

Mitochondrial dysfunction is a common hallmark of ageing-related diseases involving neurodegeneration. Huntington's disease (HD) is one of the most common monogenetic forms of neurodegenerative disorders and shares many salient features with the major sporadic disease of neurodegeneration, such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Parkinson's disease (PD). Recent evidence Read More

Aging has been a subject of interest since primordial times. More recently, it became clear that aging is the major known risk factor for several neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease. A major focus in the field of aging is to examine whether the genetic regulators of lifespan also regulate the trigger and/or progression of age-related disorders. Sirtuins, which Read More

It is well known that calorie restriction (CR) can retard the aging process in organisms ranging from yeast to non-human primates, and delay the onset of numerous age-related diseases including neurodegenerative disorders. Translation of the knowledge gained from CR research in animal models to disease prevention strategies in humans should provide therapeutic approaches for these diseases. Signaling pathways induc Read More

Cancer is caused by alterations in oncogenes, onco-suppressor genes and micro-RNA genes. These alterations are either genetic or epigenetic. Most genetic lesions of cancer are acquired, somatic events, although germ-line mutations can predispose to heritable or familial cancers. Cancer cells accumulate several genetic alterations, including chromosomal abnormalities and mutations in the nucleotide sequence of DNA. Us Read More

Normal human cells replicate their DNA with exceptional accuracy. It has been estimated that approximately one error occurs during DNA replication for each 109 to 1010 nucleotides polymerized. In contrast, malignant cells exhibit multiple chromosomal abnormalities and contain tens of thousands of alterations in the nucleotide sequence of nuclear DNA. To account for the disparity between the rarity of mutations in no Read More

Based on the gene and pathway centric concept of cancer, current approaches to cancer drug treatment have been focused on key molecular targets specific and essential for cancer progression and drug resistance. This approach appears promising in many experimental models but unfortunately has not worked well in the vast majority of cancers in clinical settings. Many new proposals, based on the same rationale o Read More

One of the main reasons why most patients with advanced cancer are not curable with the therapies available is the broad heterogeneity of cancer cells, inherently related to their genomic instability that reflects defects of cell cycle checkpoints and DNA mismatch repair (MMR). The present paper reviews today's knowledge of MMR. Microsatellite (DNA repetitive sequences) instability (MSI) used as a surrogate marker of MMR Read More

Aneuploidy is one of the major hallmarks of cancer cells and several paths towards aneuploidy have been described. However, the relevance for tumor initiation or progression and how tumors deal with the initial aneuploidy related stress response is still unclear and recent results suggest that aneuploidy can even have tumor suppressive effects under certain conditions. The molecular mechanisms leading to and sustaining gro Read More

During the process of tumorigenesis, certain cancers are known to develop deficiencies in one or more major pathways of DNA damage repair, rendering them critically dependent on alternative repair processes for maintaining genomic integrity and viability. Targeting these alternative DNA repair mechanisms is a potentially highly-specific anticancer strategy, as their inhibition is theoretically toxic only to tumor cells and not Read More

Multiple karyotypic abnormalities and chromosomal instability are characteristic features of many cancers that are relatively resistant to chemotherapeutic agents currently used in the clinic. These same features represent potentially targetable “states” that are essentially tumor specific. The assessment of the chromosomal state of a cancer cell population may provide a guide for the selection or development of Read More