Neurodegeneration neuronal receptors

However, overactivation of AMPA or KA receptors can also lead to intracellular Ca2+ overload and neurodegeneration. This maybe especially true under conditions where NMDA-receptor activity is reduced by extracellular acidity or a buildup of extracellular Zn2+ [ 12]. It is also true with respect to specific neuronal subpopulations that express AMPA-sensitive Ca2+ channels (see Ch. 15). G-protein-linked metabotropic glutamate receptors (mGluRs) appear not to mediate excitotoxicity directly but, rather, to modify the degree of excitotoxic injury. 

It is well known that prolonged NMDA glutamate receptor activation results in degeneration of neurons (excitotoxicity). This has been attributed to a large increase in calcium influx, which activates the calmodulin-dependent NOS-1 and leads to sustained elevation of nitric oxide concentrations. The increase in neurodegeneration caused by excitatory amino acids may be due to enhanced oxygen radical formation since superoxide dismutase has a beneficial effect in... 

Rohatgi T, Sedehizade F, Reymann KG, Reiser G. Protease-activated receptors in neuronal development, neurodegeneration, and neuroprotection Thrombin as signaling molecule in the brain. Neuroscientist 2004 10 501-512. 

To provide an insight into the pathways involved in HD neurodegeneration, gene expression studies of the striatum were performed on the mouse model of HD, R6/2, which expresses exon 1 of the HD gene with 140 150 CAG repeats under control of the HD promoter [70], Eighty percent of cells in the mouse striatum were estimated to consist of medium spiny GABAergic neurons. Decreased neurotransmitter receptor gene expression was identified... 

Many reports correlate the increased expression of caspases and the presence of cleaved caspases with certain types of degenerative diseases but the causal link has not been shown. For example, the increased expression of caspase-1, -2, -3, -5, -6, -7, -8, and -9 have been reported in AD (Chan and Mattson, 1999 LeBlanc et al., 1999 Lu et al., 2000 Pompl et al., 2003), caspases-3, -8 and -9 in PD (Anglade et al., 1997), caspases-1 and -3 in ALS (Pasinelli et al., 1998), and caspases-1 and -8 in HD (Sanchez et al., 1999). Altered expression levels of receptors and death ligands suggest a role for death pathways in these disorders. It has been reported that an increase in Fas expression may be harmful to both neurons and glia, and has been associated with neurodegeneration in diseases such as AD, PD, ALS, and HD (Barone and Parsons, 2000 Ugolini et al., 2003). 

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