Longo Lab Research Projects
We study the underlying signaling mechanisms that cause neurodegenerative diseases, including Alzheimer’s, Huntington’s, and tauopathies. Neurotrophin receptors (p75, TrkA, TrkB, TrkC) can promote resilience to neurodegenerative pathology by counteracting degenerative signaling and preserving synaptic function. To harness these effects, we developed a novel class of small molecule neurotrophin receptor ligands. These compounds mitigate memory and motor deficits and neuronal and synaptic degeneration in multiple mouse models and one has shown promise in a phase 2a human clinical trial for mild-to-moderate Alzheimer's disease. We are now investigating the cellular and molecular mechanisms behind these and other small molecules directed to other mechanistic targets, and developing imaging and fluid biomarkers to monitor target engagement and treatment response in both preclinical and clinical settings.
