4-(Azolyl)-Benzamidines as a Novel Chemotype for ASIC1a Inhibitors.

Acid-sensing ion channels (ASICs) play a key role in the perception and response to extracellular acidification changes. These proton-gated cation channels are critical for neuronal functions, like learning and memory, fear, mechanosensation and internal adjustments like synaptic plasticity. Moreover, they play a key role in neuronal degeneration, ischemic neuronal injury, seizure termination, pain-sensing, etc.

Integrated workflow for the identification of new GABA R positive allosteric modulators based on the in silico screening with further in vitro validation. Case study using Enamine's stock chemical space.

Numerous studies reported an association between GABA R subunit genes and epilepsy, eating disorders, autism spectrum disorders, neurodevelopmental disorders, and bipolar disorders. This study was aimed to find some potential positive allosteric modulators and was performed by combining the in silico approach with further in vitro evaluation of its real activity. We started from the GABA R-diazepam complexes and assembled a lipid embedded protein ensemble to refine it via molecular dynamics (MD) simulation.

Recording electrical activity from the brain of behaving octopus.

Octopuses, which are among the most intelligent invertebrates, have no skeleton and eight flexible arms whose sensory and motor activities are at once autonomous and coordinated by a complex central nervous system. The octopus brain contains a very large number of neurons, organized into numerous distinct lobes, the functions of which have been proposed based largely on the results of lesioning experiments. In other species, linking brain activity to behavior is done by implanting electrodes and directly correlating electrical activity with observed animal behavior.

Triggering of Major Brain Disorders by Protons and ATP: The Role of ASICs and P2X Receptors.

Adenosine triphosphate (ATP) is well-known as a universal source of energy in living cells. Less known is that this molecule has a variety of important signaling functions: it activates a variety of specific metabotropic (P2Y) and ionotropic (P2X) receptors in neuronal and non-neuronal cell membranes. So, a wide variety of signaling functions well fits the ubiquitous presence of ATP in the tissues.

Acid-Sensing Ion Channels: Focus on Physiological and Some Pathological Roles in the Brain.

Acid-sensing ion channels (ASICs) are Na+-permeable ion channels activated by protons and predominantly expressed in the nervous system. ASICs act as pH sensors leading to neuronal excitation. At least eight different ASIC subunits (including ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, ASIC4, ASIC5) are encoded by five genes (ASIC1-ASIC5).