The objective of this study is to determine the sequence of an mRNA (1.7 kb) detected in the monkey brain, thanks to its similarity to trkA mRNA (3.2 kb), which encodes the high affinity receptor for nerve growth factor (NGF). NGF actions, via the trkA receptor, sustain the survival and functions of select populations of neurons. Cholinergic neuronal loss and deterioration of the basal forebrain is associated with Alzheimer's disease. As cholinergic neurons are heavily endowed with the trkA receptor and are thought to be dependent on NGF trophic support, a defect in NGF signaling may therefore be important in Alzheimer's disease. An mRNA with sequence similarity to the trkA receptor could encode a protein that contributes to NGF signaling. An extensive search of a rhesus cDNA library (made from the RNA of 2 monkeys) failed to identify the cDNA that corresponds to the 1.7 kb mRNA. Polymerase chain reaction (PCR) was used (RNA samples of 4 monkeys) to generate cDNA templates to investigate the unknown mRNA. Northern blot analysis (RNA samples of 6 monkeys) and RNase protection assay using the same cRNA probe (template generated by PCR) showed that while the 1.7 kb mRNA is similar to that for trkA, the sequences are not identical. Furthermore, we determined that the unknown mRNA may have an NGF binding-like motif. The presence of an NGF binding-like motif would suggest that this mRNA does code for a protein capable of binding NGF and, thus, be important in NGF signaling and basal forebrain function.
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