Toxic Aß oligomers attach to membrane receptors and form channels in the membranes of different types of neuronal and neurosensory cells, such as retinal ganglion cells (RGCs), retinal pigment epithelium (RPE) cells and hippocampal neurons, causing them to lose their electrical membrane potential and eventually killing them. This is common to various neurodegenerative diseases such as glaucoma, AMD or Alzheimer`s disease.
Results from a patch-clamp experiment in RGCs from mice cultivated for 5-7 days demonstrate the potential for being measured as indicator for the toxic effect of increasing concentrations of Aβ oligomers. A concentration of only 44 nmol/l Aβ kills 50% of the cells in culture (Fig. 3).
In cell culture experiments, a moderate concentration (50 nmol/l) of Aβ was administered to the cultures of the different cell types shown (Fig. 4, grey bars). This reduced the membrane potential (or a similar electrophysiological parameters like long term potentiation) significantly but did not kill the cells immediately. The three different cells types shown represent the main cells affected in neurodegenerative diseases: glaucoma (retinal ganglion cells), dry AMD (retinal epithelium cells), and Alzheimer’s disease (hippocampal neurons). As seen in each case, pre-incubation with GAL-101 counteracted the toxic effect significantly.