Rubén HERVAS MILLAN, PhD | The University of Hong Kong;
Competition Sponsor: Research Grants Council of the Hong Kong Special Administrative Region, China
Award Year: 2024
Long-lasting memories involve converting temporary experiences into persistent changes in synaptic function. These changes depend on modifications in the synaptic proteome. Molecular chaperones serve as an interface between the environment and the proteome. Among the chaperone families, J-domain proteins (JDPs) have specific and diverse capabilities in regulating protein states. Recently, we manipulated the expression of 31 JDPs in a subset of neurons in the Drosophila melanogaster central brain. We identified a previously uncharacterized JDP, which we named Funes, that enhances long-term memory by acting on odor-responsive Kenyon cells and reward-responsive dopaminergic PAM neurons. Mechanistically, Funes improves memory by facilitating the amyloid aggregation of the cytoplasmic polyadenylation element binding (CPEB) protein, Orb2 in Drosophila, which serves as a physical substrate for memory by promoting the translation of memory-related genes (Patton et al, under review – Cell). Surprisingly, this suggests that promoting certain types of amyloids – protein structures often associated with diseases like Alzheimer’s – may aid, rather than hinder, memory. However, it is unclear whether this finding applies to humans, where, similarly to Drosophila, CPEB forms functional aggregates. In the “Healthy Longevity Catalyst Awards 2024,” we aim to investigate the innovative idea that molecular chaperones regulate memory in humans. If this is true, identifying modulators could have commercial and therapeutic value. This discovery could lead to the development of strategies to enhance memory in Alzheimer’s patients or the elderly population.