Novel mechanisms of gene expression in developing mammalian neurons

A family of proteins called neurotrophins helps build the developing brain, and a lack of them may contribute to Alzheimer's disease. For 50 years, scientists have known that neurotrophins support brain development, learning, memory, and nerve regeneration after injury. In Alzheimer's patients, neurotrophin activity in the brain is significantly reduced. A recent clinical trial found that delivering one neurotrophin—nerve growth factor (NGF)—directly to the brains of Alzheimer's patients triggered dramatic neuronal regeneration and improved cognitive performance. This project aims to understand exactly how neurotrophins switch on genes in developing neurons, and to identify new proteins that promote neuronal development in mammals. This is fundamental science: it seeks to uncover the molecular machinery that translates a neurotrophin signal into a change in gene expression. If successful, the work could reveal new targets for drugs that mimic or boost neurotrophin activity. That could lead to therapies that prevent or slow neurodegenerative diseases such as Alzheimer's, which will become an increasing burden as populations age. The immediate payoff is a deeper understanding of how the brain wires itself—knowledge that has historically led to unexpected clinical breakthroughs.