Screening of Novel Synthetic Compounds and Marine Extract Libraries in In Vitro and In Vivo Models of Motor Neuron Disease (MND/ALS) for Discovering New Potentially Therapeutic Neurotrophin Mimetics

Neurotrophins are a class of polypeptides able to recover and improve neuronal function during neurodegenerative conditions. The challenges of developing neurotrophins as clinical candidates have limited their potential therapeutic use. A solution to overcome these issues is the development of neurotrophin mimetics that mimic endogenous neurotrophins.
Aims and Objectives: 1) Screening three libraries of compounds or marine extracts to identify therapeutic molecules promoting motor neuronal survival in co-culture i-astrocytes derived from a panel of ALS patient lines. 2) Isolate and characterize the constituents of the top hit extracts and test their efficacy on the co-culture assay. 3) Perform in silico screening to predict which top hits can be potential small neurotrophin mimetics. 4) Understand the molecular mechanisms of the top hits. 5) Test the therapeutic efficacy of the top hits in ALS C9ORF72 zebrafish models.