Use of neuregulin-β as an indicator and/or target
The invention relates, inter alia, to the use of neuregulin-β as a target in a screening method for active compounds, in particular for exerting an influence on changes in calcium concentration which are mediated by glutamate receptors. The invention furthermore relates to the use of neuregulins, preferably a neuregulin isoform having an isoelectric point in the range from pH 4.3 to 5.0, as a target for detecting and/or exerting an influence on neuronal processes, in particular for exerting an influence on long-term memory. Neuregulins, in particular neuregulin-β and also substances which exert an influence on the status, i.e. the expression and/or post-translational modification, of neuregulin-β, can therefore be used as agents for controlling the course of, treating and/or alleviating neuronal diseases, e.g. Alzheimer's disease.
1. An isolated neuregulin-β isoform, having an isoelectric point (pI) in the range from about pH 4.3 to 5.0, wherein said neuregulin-β isoform has an apparent molecular mass of about 32 kd as determined using SDS-PAGE and comprises amino acids 88-94 according to SEQ ID NO:4, and
wherein said isolated neuregulin-β isoform is obtainable from mammalian hippocampal cells using isoelectric focusing employing immobilized, nonlinear pH gradients from 3 to 10 and linear gradients of from 4 to 7 as a first dimension and SDS-PAGE (12% acrylamide) as a second dimension in two dimensional PAGE.
2. The neuregulin-β isoform as claimed in claim 1 having a pl in the range from about pH 4.5 to 4.7.
3. The neuregulin-β isoform as claimed in claim 1 , wherein said neuregulin-β isoform reacts with anti-neuregulin-β antibodies.
4. The isolated neuregulin-β isoform according to claim 1 , wherein said mammalian hippocampal cells are rat or human hippocampal cells.
5. The isolated neuregulin-β isoform according to claim 1 , wherein said mammalian hippocampal cells are pre-natal or neonatal cells.