Current Drug Targets - Volume 5, Issue 6, 2004

Neurofibrillary degeneration (ND) is both a pivotal and a primary lesion of Alzheimer disease (AD) and related tauopathies. To date in all known tauopathies including AD, the neurofibrillary changes, whether of paired helical filaments (PHF), twisted ribbons or straight filaments (SF) are made up of abnormally hyperphosphorylated tau, and the number of these lesions directly correlates to the degree of dementia in the affecte Read More

Alzheimer's disease (AD) is characterized histopathologically by β-amyloid-containing plaques, neurofibrillary tangles (NFT), reduced synaptic density, and neuronal loss in selected brain areas. Plaques consist of aggregates of a small peptide termed Aβ which is derived by proteolysis of the larger amyloid precursor protein APP, whereas NFT are composed of hyperphosphorylated forms of the microtubule-associated protein Read More

Alzheimer's disease (AD) is a progressive senile dementia characterized by deposition of a 4 kDa peptide of 39-42 residues known as amyloid beta-peptide (Aβ) in the form of senile plaques and the microtubule associated protein tau as paired helical filaments. Genetic studies have identified mutations in the Aβ precursor protein (APP) as the key triggers for the pathogenesis of AD. Other genes such as presenilins 1 and 2 (PS1 Read More

Inflammation has been reported in numerous neurodegenerative disorders such as Parkinson's disease, stroke and Alzheimer's disease (AD). In AD, the inflammatory response is mainly located to the vicinity of amyloid plaques. Cytokines, such as Interleukin-1 (IL-1), Interleukin-6 (IL-6), Tumor Necrosis Factor alpha (TNF-α) and Transforming Growth Factor beta (TGF-β) have been clearly involved in this inflammatory process. Alt Read More

Alzheimer's disease (AD) has become linked to inflammation and metal biology. Metals (copper, zinc and iron) and inflammatory cytokines are significant factors that increase the onset of sporadic late onset forms of the dementia. The genetic discovery that alleles in the hemochromatosis gene accelerate the onset of disease by five years [1] has certainly validated interest in the metallobiology of AD as originally described Read More

A growing wealth of evidence indicates that the key pathological event in Alzheimer's disease is the conversion of the normal soluble amyloid-β peptide into β-sheet-rich oligomeric structures which have a neurotoxic activity and ability to form insoluble amyloid deposits that accumulate in the brain. b-sheet breakers constitute a new class of drugs that are designed to specifically bind amyloid-β peptide and block and / or re Read More

In this review, we discuss the role of cell cycle dysfunction in the pathogenesis of Alzheimer disease and propose that such mitotic catastrophe, as one of the earliest events in neuronal degeneration, may, in fact, be sufficient to initiate the neurodegenerative cascade. The question as to what molecule initiates cell cycle dysfunction is now beginning to become understood and, in this regard, the gender-predication, age-related Read More

Glucagon-like peptide-1 (7-36)-amide (GLP-1) is an endogenous 30-amino acid gut peptide, which binds at the GLP-1 receptor coupled to the cyclic AMP second messenger pathway. GLP-1 receptor stimulation enhances pancreatic islet β-cell proliferation, glucose-dependent insulin secretion and lowers blood glucose and food intake in patients with type 2 diabetes mellitus. Not limited to the pancreas, the chemoarchitecture of GL Read More

In the recent years it has been increasingly recognized that pharmacogenetical factors play an important role in the drug treatment. These factors may influence the appearance of side-effects and drug interactions due to interindividual differences in the activity of metabolizing enzymes. Risperidone in humans is mainly metabolized to 9-hydroxyrisperidone by the polymorphic cytochrome enzyme P450 2D6 (CYP2D6). Plas Read More

The inflammatory response of the lung and airways is one of the main targets for the development of new therapies for variety of disorders including the acute respiratory distress syndrome, cystic fibrosis, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease. Over the last decade our understanding of the molecular biology of the inflammatory response has advanced considerably and has opened u Read More