Objective: The aim of the present study was to further elucidate the role of Engrailed in dopamine neurotransmission.

Background: Engrailed1 and Engrailed2, collectively Engrailed, are transcription factors of the homeoprotein family. Engrailed is expressed in mesencephalic dopaminergic neurons throughout the entire life span and plays an important role in the survival of this neuronal population. It has also been proposed that Engrailed enhances dopamine synthesis, but this has not yet been investigated in detail and only hypotheses exist about the underlying mechanisms.

Methods: We treated iPS cell-derived TH positive neurons from healthy individuals and primary rat midbrain neuronal cultures with recombinant Engrailed and measured the levels of dopamine and of its metabolites. Additionally, we measured the mitochondrial form factor in the presence or absence of Engrailed.

Results: Our data provide evidence that Engrailed influences DA synthesis both in primary mesencephalic neurons and in iPS-cell derived neurons. This increase in intracellular dopamine is not related to an increase in tyrosine hydroxylase protein levels and is also observed in (nor)adrenergic cells. Future studies are warranted exploring the underlying mechanism, which may include posttranslational modification of TH.

Conclusions: Taken together, data support the idea of a possible role of Engrailed as a therapeutic agent in the treatment of Parkinson’s disease with roles in both dopamine synthesis and mitochondrial morphology.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/engrailed-enhances-dopamine-synthesis-in-healthy-dopaminergic-neurons/