Identification of Compounds Targeting HuD. Another Brick in the Wall of Neurodegenerative Disease Treatment

ELAV-like
(ELAVL) RNA-binding proteins play a pivotal role in post-transcriptional
processes, and their dysregulation is involved in several pathologies.
This work was focused on HuD (ELAVL4), which is specifically expressed
in nervous tissues, and involved in differentiation and synaptic plasticity
mechanisms. HuD represents a new, albeit unexplored, candidate target
for the treatment of several relevant neurodegenerative diseases.
The aim of this pioneering work was the identification of new molecules
able to recognize and bind HuD, thus interfering with its activity.
We combined virtual screening, molecular dynamics (MD), and STD-NMR
techniques. Starting from around 51 000 compounds, four promising
hits eventually provided experimental evidence of their ability to
bind HuD. Among the selected best hits, folic acid was found to be
the most interesting one, being able to well recognize the HuD binding
site. Our results provide a basis for the identification of new HuD
interfering compounds which may be useful against neurodegenerative
syndromes.