Cell non-autonomous functions of homeoproteins in neuroprotection in the brain

Homeoproteins transcription factors can transfer between cells and play important roles in development. However, some of these homeoproteins are expressed in the adult, but their function is unknown. The loss of mesencephalic dopaminergic (mDA) neurons is the cause of Parkinson's disease. In mice lacking a functional allele for the Engrailed 1 homeoprotein, mDA neurons progressively die starting about 6 weeks after birth. Infusion of recombinant Engrailed stops the death of these neurons demonstrating that homeoproteins can be neuroprotective. This has been extended to retinal ganglion cell neurons (RGCs), which die in glaucoma and optic neuropathies. The homeoprotein Otx2 promotes the survival of injured adult RGCs both in vitro and in vivo. These examples raise the possibility that homeoproteins may provide neuroprotection to neurons vulnerable in other neurodegenerative diseases.