Current Medicinal Chemistry - Central Nervous System Agents - Current Issue

Alzheimer's disease (AD) is one type of dementing central nervous amyloidosis characterized by two different types of fibrillar deposits, namely senile plaques and neurofibrillary tangles. Amyloid-β-proteins (Aβ) are the major constituents of senile plaques. The aggregation of soluble Aβ into insoluble amyloid fibrils is believed to be an important step in the pathogenesis of AD and the prevention of this process therefore seem Read More

A broad overview of neurotoxins is presented based on electron transfer, reactive oxygen species, and oxidative stress. Although mode of action is complex, these aspects evidently play an important role in many cases. It is relevant that metabolites from toxins generally possess electron transfer functionalities which can participate in redox cycling. Much evidence exists in support of the theoretical framework. Toxic effect Read More

Currently, a handful of FDA approved drugs are commercially available to treat Alzheimer's disease (AD). Among these, Tacrine (Cognex), Donepezil (Aricept), Rivastigmine (Exelon), Galantamine (Reminyl) and Memantine (Nemenda; Forest) are either acetylcholinesterase or N-methyl-D-aspartate antagonists. These are only palliative solutions, however, and side effects remain an important concern. Clearly, the search for more po Read More

Alzheimer's disease (AD) is triggered by the pathophysiological cleavage of a single transmembrane glycoprotein denominated amyloid β-protein precursor (AβPP) rendering amyloid β-peptide (Aβ) that aggregates in β- sheets forming the neuritic plaques. Since AbPP is playing a key role in AD development, this review will be focused in the structure, proteolytic processing, related secretases, mutations, localization and physiolo Read More

The life cycle of a protein consists of highly regulated stages of synthesis, maturation, activity, and degradation. The last stage of this cycle frequently occurs through the ubiquitin-proteasome system, which tags and destroys proteins in the cell. Work in recent years regarding the ubiquitin-proteasome system has extended into the field of neurobiology, where the system is critical for proper neuronal function. In thi Read More

Several lines of evidence suggest a role for oxidative cascades of events leading to neurodegeneration associated with Parkinson's, Alzheimer, Huntington diseases, and amyotrophic lateral sclerosis. In agreement with the notion of oxidative/nitrosative involvement in these chronic diseases, in vivo models of disease as well as biochemical and epidemiological evidence suggest a neuroprotective role for natural antioxidant pol Read More