REAKTHROUGHS IN BASIC BIO-medical sciences, including human genomics, stem cell biology, biomedical engineering, molecular biology, and immunology, over the past 5 decades have provided an unprecedented supply of information for improving human health. This revolutionary progress in basic science would not have happened without the public's long-term investment in and steadfast commitment to basic biomedical research. Translating the information gained through these basic discoveries into knowledge that will affect clinical practice and, ultimately, human health requires clinical research involving human subjects and human populations, as well as devel-opment of improved health services based on that research. This next scientific frontier deserves a correspond-
Alzheimer (3/A4 amyloid precursor protein (APP) has been suggested to play a central role in the pathogenesis of Alzheimer disease. We have measured the content of different species of APP holoprotein and carboxyl-terminal fragments in human brains from young individuals, nondemented aged individuals, and aged individuals with Alzheimer disease. By using an antibody directed against the cytoplasmic domain of APP, five species were resolved. Three of these, of molecular masses 106, 113, and 133 kDa, represent presumptive immature and mature isoforms of APP holoprotein. Two smaller proteins, of molecular masses 15 and 19 kDa, represent presumptive proteolytic carboxyl-terminal fragments of APP. The 133-, 113-, 106-, and 15-kDa species were found in both grey and white matter, whereas the 19-kDa species was found only in grey matter. Total APP immunoreactivity (sum of an five species) and the levels of the 113-, 106-, and 15-kDa species were not iantiy different in brain samples from young individuals, nomdemented aged individuals, and aged individuals with Mzelmer disease. In contrast, the levels of the 133-and 19-kDa species increased 2-to 3-fold with age. A correlation was observed between the levels of the 133-and 19-kDa species, suggesting a possible precursor-product relationship.
DARPP-32 (dopamine- and cyclic AMP-regulated phosphoprotein, Mr = 32,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) is a neuronal phosphoprotein that is enriched in neurons which possess dopamine D1 receptors, particularly striatonigral neurons. In rat brain slices, the phosphorylation state of DARPP-32 is regulated by dopamine, acting through the dopamine D1 receptor and the adenylyl cyclase system. This study reports that chronic blockade (21 days) of either dopamine D1 receptors by SCH-23390 or dopamine D2 receptors by raclopride does not affect the concentrations of DARPP-32 in specific rat brain regions (striatum, thalamus, hippocampus, frontal cerebral cortical pole). Northern blot analysis indicates that the steady-state level of DARPP-32 mRNA in striatum is also unchanged by these treatments.
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