Imbalanced modulation of protein acetylation and proteasomal degradation in Familial
Familial Dysautonomia (FD) is an autosomal recessive developmental disorder of the peripheral nervous system (PNS). Pathology studies of FD patients have revealed abnormal development, survival and progressive degeneration of the sensory and autonomic PNS. FD is a result of a point mutation in the IKBKAP gene, leading to a severe reduction of the IKAP/Elp1 protein. IKAP/Elp1 is a scaffold protein in the six subunits elongator complex, which is a histone acetyl transferase component of RNA polymerase II and is involved in transcriptional elongation. The cytoplasmic function of IKAP/Elp1 in neurons is still controversial.Preliminary study results showed interacted influences protein deacetylase and proteasomal inhibitors on cells survivor in a cell model of FD from neuroblastoma origin.
My project hypothesis is that imbalanced modulation of protein acetylation and proteasomal degradation is involved in the mechanism underlying the pathology in FD, and might be used as a possible target for disease modifying interventions.
Swift Oral Presentation on ISFN 2016
Research Categories: Cell research, Molecular biology, Neurodegenerative disease, Neurodegenerative disorders, Personalized medicine