Current Pharmaceutical Design - Volume 11, Issue 26, 2005

Alzheimer's Disease (AD) and its associated morbidity continues to be a devastating condition for patients afflicted with this ailment, as well as the family and caregivers of patients. Although great strides have been made with respect to understanding the etiology associated with AD, it still remains a large unmet medical need, affecting nearly one in ten individuals over the age of 65, and nearly one in two persons by age 85 Read More

An effective treatment for age-related cognitive deficits remains an unmet medical need. Currently available drugs for the symptomatic treatment of Alzheimer's disease or other dementias have limited efficacy. This may be due to their action at only one of the many neurotransmitter systems involved in the complex mechanisms that underlie cognition. An alternative approach would be to target second messenger systems tha Read More

There is extensive evidence that changes in immune system activation accompany the pathological changes of Alzheimer's disease (AD), but a mechanistic understanding of how the immune system actually participates in disease pathogenesis is still largely lacking. Because of the complexity of the immunological response, and the difficulty in identifying the key molecular players that underlie any given immunologi Read More

One of the consistent findings in the brains of Alzheimer's Disease (AD) patients is loss of cholinergic function. The cholinergic approach to treatment of AD involves counteracting this loss in cholinergic activity by pharmacological intervention to increase cholinergic transmission. The cognitive effects of acetylcholine are mediated via the muscarinic M1 receptor. Direct stimulation of this receptor using muscarinic M1 a Read More

An effective, disease-modifying treatment of Alzheimer's disease (AD) remains one of the most significant unmet needs in modern medicine. As a result of the extensive research in the area, the mechanisms underlying the disease are now much better understood than at any time before. A significant amount of evidence points to the central role of β-amyloid (Aβ) peptide-mediated toxicity in the disease etiology and strategi Read More

Dementia caused by Alzheimer's disease is a large medical burden on society in the developed world. Current treatments are largely symptomatic, and there is an urgent need for therapies which can interrupt or reverse the progression of disease. A number of strategies for intervention are being actively pursued; among the most promising is the inhibition of β-secretase, or BACE. BACE is the enzyme responsible for N-termi Read More

RNAi (RNA interference) was originally detected in Caenorhabditis elegans as biological response to exogenous double-stranded RNA (dsRNA), which induces very effective sequence-specific silencing of gene expression. Further investigations revealed that RNAi can occur in many eukaryotic species. Increasing understanding of the biochemical components of RNAi indicates the existence of a conserved machinery for dsRNA-i Read More

The endocannabinoid system has been involved in the control of several neurophysiological and behavioural responses. Indeed, recent studies have suggested that the cannabinoid system could represent an important substrate for the control of emotional behaviour, and further research would probably help to identify new promising therapeutic targets. This paper reviews the results obtained in different animal models used to i Read More

Eicosanoids are potent biologically active arachidonic acid-derived lipid mediators that are intimately involved in inflammation and cancer. Cyclooxygenase (COX), the key enzyme in prostaglandin (PG) biosynthesis, controls one of the major pathways of arachidonic acid metabolism and is the main target for non-steroidal anti-inflammatory drugs (NSAIDs). COX exists in two distinct isoforms, COX-1 and COX-2, the latter b Read More

Acute myelogenous leukemia (AML) is a difficult disease to treat, and better treatments are needed. Molecular targeted therapy represents a novel therapeutic approach. The FLT3 tyrosine kinase receptor is mutated in approximately one-fourth to one-third of patients with AML. Normally, binding of FLT3 ligand to the FLT3 receptor leads to phosphorylation of tyrosine residues and activation of the receptor. This in turn leads Read More