Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease, among others, are a prevailing medical challenge with woefully inadequate therapeutic options.  Current medicinal treatments focus primarily on modulating neurotransmitter levels, which have resulted in modest cognitive benefits and do not impact life expectancy outcomes.  An attractive alternative may lie in the potential of neurotrophic natural products, of which there are over a hundred known examples.  Our research has begun investigating the activity and mode of action of phenylbutenoid dimers called banglenes, which are isolated from Javanese ginger.  These molecules are orally bioavailable, and have been demonstrated to increase neurogenesis in mice, as well as increased neurite outgrowth and viability in primary rat neuron cell culture.  We have synthetically produced trans-banglene and have performed structure-activity relationship studies.  Further, a global proteomic analysis has highlighted iron-binding and iron storage proteins as being altered in expression level in response to trans-banglene treatment.  This is notable, as iron dyshomeostasis is a hallmark of many neurodegenerative disease profiles and is connected to the development of protein aggregates such as amyloid β, tau, and Lewy bodies.  This talk will explore this relationship, preliminary results to date, and will outline our future work and ultimate aim to identify recognition partners in the cell and the full mechanism of action for trans-banglene.