Current Medicinal Chemistry - Central Nervous System Agents - Volume 5, Issue 3, 2005

The main component of the amyloid plaque is insoluble Aβ1-42 (Aβ42), which adopts a structure rich in antiparallel β-pleated sheets. Recently, increasing awareness of Aβ intermediates as molten-globule states has paralleled insight into the biological activities of the Aβ conformer. The molten-globule state of Aβ42 displays a less ordered, metastable conformation that is stabilized by the formation of fibrils. The molten-g Read More

Deficient inhibitory processing of the P50 auditory evoked potential is a measurable marker observed in schizophrenia. Several lines of evidence suggest that α7 nicotinic receptors (α7 nAChRs) play a critical role in P50 auditory sensory gating in the human brain. Similar to schizophrenic patients, DBA/2 mice spontaneously exhibit a deficit in inhibitory processing of the P20-N40 auditory evoked potential, which is a rodent Read More

Advances in combinatorial synthesis and high throughput screening have resulted in libraries containing hundreds of thousands of drug candidate compounds. Computational prediction of properties that will determine the utility of a drug molecule has become a sine qua non in the pharmaceutical industry, because of the appreciation that ADMET properties must be considered early in the discovery process and the Read More

There is evidence suggesting that nitric oxide (NO) may play an important role in dopamine (DA) cell death. NO may act as a neuroprotector or neurotoxic agent in dopamine neurons, depending on cell redox status. Glutathione (GSH) depletion is the earliest biochemical alteration shown to date in brains of Parkinson's disease (PD) patients. However, data from animal models show that GSH depletion by itself is not sufficient Read More

The accumulation of high local concentrations of excitatory amino acids, particularly glutamate, is involved in neuronal cell death in neurodegenerative diseases such as stroke, trauma, Huntington's disease, and amyotrophic lateral sclerosis. Accumulation of glutamate leads to excessive Ca2+ influx into the neuron. The molecules involved in neuronal degeneration following intracellular Ca2+ overload have bee Read More

Gamma-aminobutyric acid (GABA) is the most important inhibitory transmitter in the central nervous system. Most of the actions of GABA are mediated by GABAA receptors. These are choride ion channels that can be opened by GABA and can be modulated by a variety of pharmacologically and clinically important drugs. GABAA receptors are composed of five subunits that can belong to different subunit cl Read More