ligand gated ion channel.ppt

Huntington's disease Huntington's disease (HD) is an inherited neurodegenerative disorder affecting cognition, motor function and mood hypothesis: excitotoxicity * 1. In R6/2 and YAC128 HD mouse models, tryptophan metabolites that increase oxidative stress (3-hydroxykynurenine, 3-HK) or directly activate NMDARs (quinolinic acid, QUIN) were increased in cortical and/or striatal tissue in the early symptomatic stages Measurements of NMDA-evoked currents in striatal slices from symptomatic R6/2 mice indicated larger mean peak current densities mediated by NMDARs as well as altered NMDAR sensitivity to modulation by extracellular magnesium A specific enhancement of NR2B-containing NMDARs by mhtt may contribute to cognitive deficits found in HD Aberrant NMDAR activity in HD * * Neurobiology of Disease 23 (2006) 190 – 197 neostriatum Frontal cortex cerebellum * Neurobiol Dis. 2006 Jul;23(1):190-7. Epub 2006 May 12 * Neurobiology of Disease 23 (2006) 190 – 197 * J Neurosci Res. 2005 Nov 1;82(3):377-86 Fig. Representative neurons from WT and R6/2 least and most responsive populations and their currents at 15 days 2. Alzheimer's disease Aβ oligomers (also known as ADDLs) are known to accumulate in brain tissue of AD patients and are considered centrally related to pathogenesis. 2. ADDLs stimulated excessive formation of reactive oxygen species (ROS) through a mechanism requiring N-methyl-D-aspartate receptor (NMDA-R) activation 3. Memantine, an open channel NMDA-R antagonist prescribed as a memory-preserving drug for AD patients, completely protected against ADDL-induced ROS formation, as did other NMDA-R antagonists. * Evidence * * According to their ionic permeabilities and the neurotransmitter LGICs are subdivided : The γ-amino butyric acid receptors (GABAAR) Glycine receptors (GlyR) { Anion-selective { Nicotinic acetylcholine receptors (nAChRs) Glutamate(GluR) receptor Purinergic (P2X) receptor Serotoninergic (5HT3) receptor Cat