Role of HuD in nervous system function and pathology

Hu proteins are a family of RNA-binding proteins (RBPs) that are homologs of Drosophila ELAV, a protein required for nervous system development. Three of these proteins (HuB, HuC, and HuD) are primarily expressed in neurons. The fourth member, HuR is ubiquitously expressed in all tissues. At the molecular level, Hu proteins are known to interact with AU-rich instability conferring sequences in the 3' UTR of specific target mRNAs, stabilizing the mRNAs. These proteins are not only the best known mRNA stabilizers but also the earliest markers of the neuronal cell lineage. Among the neuronal Hu proteins, HuD has been shown to accelerate neuronal differentiation and axonal outgrowth in neurons both in culture and in vivo. In addition, HuD and other Hu proteins participate in synaptic plasticity mechanisms in the mature central nervous system and promote regeneration of peripheral nerves. Furthermore, HuD has been implicated in pathological conditions from neurodegenerative disorders such as Parkinson's and Alzheimer's disease to childhood brain tumors. This review will focus on the involvement of HuD in nervous system function and pathology.