Current Alzheimer Research - Volume 2, Issue 3, 2005

Existing cholinesterase (ChE) inhibitor therapies for Alzheimer's disease (AD), while effective in improving cognitive, behavioral and functional impairments, do not alter disease progression. Novel drug design studies have focused on the classical ChE inhibitor, (-)-physostigmine, producing alterations in chemical composition and threedimensional structure, which may offer an improved therapeutic index. The phenylcarbam Read More

Current mouse models of Alzheimer's disease show brain pathology that correlates to a degree with memory impairment, but underlying molecular mechanisms remained unknown. Here we report studies with three lines of transgenic mice: animals that doubly express mutated human amyloid precursor protein (APPswe) and human acetylcholinesterase (hAChE); and animals transgenic for only the APPswe or the hAChE. Among Read More

The cholinergic system impairment observed in Alzheimer's disease (AD) patients leads to the cognitive, global and behavioral dysfunction commonly associated with dementia. The only treatment for AD has been the use of inhibitors of acetylcholinesterase (AChE) (E.C. 3.1.1.7), which is one of the several proteins associated with amyloid plaque deposits. Recently, novel dual inhibitors of AChE have been developed that ta Read More

The cholinergic hypothesis of decline in dementia, whereby deficits in learning, memory and behavior are caused, at least in part, by decreased levels of acetylcholine (ACh) in the brain, first emerged more than 20 years ago. The role for acetylcholinesterase (AChE) and its inhibition in this scheme has long been accepted, but findings from preclinical experiments and clinical trials have placed butyrylcholinesterase (BuChE) Read More

What are the aims appropriate for a science of clinical pharmacology and clinical trials: to test drugs for efficacy and safety in the clinic, to establish the optimal effectiveness and safety of drugs in patient care or both? Current designs of clinical trials test drugs for efficacy and safety in clinical settings-they do not address the clinician's problems adequately. Clinical trials better address the effectiveness of drugs in patient care Read More

Alzheimer's disease is characterized by the extracellular deposition of the amyloid β-peptide that derives from its precursor bAPP by sequential actions of β- and γ- secretases, respectively. Recent studies aimed at identifying these enzymes have been reported as it is thougth that their inhibition should hopefully lead to reduce Aβ load in the AD brains. β-secretase seems to be due to BACE1, a novel membrane-bound as Read More

Alzheimer disease (AD) and related tauopathies are all characterized histopathologically by neurofibrillary degeneration. The neurofibrillary changes, whether of paired helical filaments (PHF), twisted ribbons or straight filaments (SF) are made up of abnormally hyperphosphorylated tau. Unlike normal tau which promotes assembly and maintains structure of microtubules, the abnormal tau not only lacks these functions b Read More

Cholesterol-induced production of amyloid beta (Aβ) as a putative neurotoxin in Alzheimer's disease (AD), along with epidemiological evidence, suggests that statin drugs may provide benefit in treatment of the disorder. We tested the effect of once daily atorvastatin calcium (80 mg; two 40mg tablets) on cognitive and/or behavioral decline in patients with mild-to-moderate AD. The study was designed as a pilot intention-t Read More

Inflammation is characteristic of a broad spectrum of neurodegenerative diseases. These include Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases, amyotrophic lateral sclerosis, all of the tauopathies, multiple sclerosis and many other less common conditions. Morphologically, the level of inflammation is determined by the concentration and degree of activation of microglial cells. Biochemically, Read More

The statement, “neurodegenerative diseases are incurable because neurons do not regenerate during adulthood,” has been challenged, and we have now found much evidence that the matured brain is capable of regenerating neurons. In our previous study, human neural stem cells (HNSCs) transplanted into aged rat brains differentiated into neural cells and significantly improved the cognitive functions of the animals, indicat Read More

Glucagon - like peptide - 1 (7-36) - amide (GLP-1) is an endogenous insulinotropic peptide that is secreted from the gastrointestinal tract in response to food. It enhances pancreatic islet β-cell proliferation, glucose-dependent insulin secretion, and lowers blood glucose and food intake in patients with type 2 diabetes mellitus. GLP-1 receptors, are coupled to the cyclic AMP second messenger pathway, and are expressed throughou Read More