Neurodegenerative diseases are characterized by a loss of nervous system function and increased levels of neuronal death. To address the underlying neurodegeneration and the failure to extend life expectancy requires alternative strategies such as promoting neuronal survival. Neurotrophins are endogenous proteins which exhibit pro-survival, pro-differentiation, and synaptic plasticity by mediating the body’s natural signaling pathways. Unfortunately, the short half-lives of neurotrophins (&lt;1 minute in serum) and inability to cross the blood-brain barrier make them non-viable as broad therapeutic applications in neurodegenerative disease therapy. Therefore, an attractive strategy is the use of small molecules that act as functional analogs to neurotrophins. One set of functional analogs of neurotrophins are the phenylbutenoid (PBD) dimers (Figure 1a). The oral bioavailability and neurotrophic activity of PBD molecules make them good therapeutic leads for neurodegenerative diseases. Recently reported data in our group further delineates the polygonal behavior of PC-12 cells with neurite projections in the absence and presence of NGF when treated with ±trans PBD (Figure 1b). Understanding the mechanism of action of PBD is crucial since it reveals the signaling pathway that initiates a neurotrophic response in neuronal cells. Therefore, the aim of the study is to investigate the mechanism of action of PBD by identifying its cellular recognition partner in a pull-down assay, in which derivatized PBD acts as a bait molecule bound to beads of a solid support. This work constitutes early steps towards therapeutic strategies to combat, and potentially reverse, neuron cell death in neurodegenerative diseases.

Investigation of mechanism of neurotorphic phenylbutenoid dimers

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.