ponazuril and Cognitive-Dysfunction

Alzheimer's disease (AD) is the most common neurodegenerative disorder and results in severe neurodegeneration and progressive cognitive decline. Neurotrophins are growth factors involved in the development and survival of neurons, but also in underlying mechanisms for memory formation such as hippocampal long-term potentiation. Our aim was to identify small molecules with stimulatory effects on the signaling of two neurotrophins, the nerve growth factor (NGF) and the brain derived neurotrophic factor (BDNF). To identify molecules that could potentiate neurotrophin signaling, 25,000 molecules were screened, which led to the identification of the triazinetrione derivatives ACD855 (Ponazuril) and later on ACD856, as positive allosteric modulators of tropomyosin related kinase (Trk) receptors. ACD855 or ACD856 potentiated the cellular signaling of the neurotrophin receptors with EC

Topics: Age Factors; Animals; Behavior, Animal; Brain; Cell Line, Tumor; Cognition; Cognitive Dysfunction; Disease Models, Animal; Humans; Male; Maze Learning; Membrane Glycoproteins; Mice, Inbred C57BL; Motor Activity; Nootropic Agents; Protein-Tyrosine Kinases; Rats, Sprague-Dawley; Receptor, trkA; Receptor, trkB; Receptors, Nerve Growth Factor; Signal Transduction; Small Molecule Libraries; Triazines