The Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, U.S.A.
Address for correspondence: Hari Manev, M.D., Ph.D., The Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, 1601 West Taylor Street, MC912, Chicago, IL 60612, U.S.A. Voice: 312-413-4558; fax: 312-413-4569.
HManev{at}psych.uic.edu
5-Lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) are two
enzymes that are critical for the synthesis of eicosanoids,
the inflammatory metabolites of arachidonic acid. Both 5-LOX
and COX-2 are expressed in the brain, including in CNS neurons.
The physiologic role of these proteins in neuronal functioning
is not clear. In non-neuronal tissues these two enzymes often
assume similar roles: in addition to their function in inflammation,
5-LOX and COX-2 appear to be associated with cell proliferation,
that is, with tumor growth. High 5-LOX expression has been noticed
in the proliferating brain or pancreatic tumor cells; reduction
in tumor cell proliferation and/or destruction of tumor cells
was achieved with 5-LOX inhibitors. Proliferation of immature
neurons/neuroblasts is an important component of mitotic neurogenesis.
We investigated the role of 5-LOX in proliferation using cultures
of human neuronal precursor cells, NT2. We found that these
cells express 5-LOX mRNA and we used
3H-thymidine incorporation
as a measure of cell proliferation; this was reduced by treating
the cultures with 5-LOX inhibitor AA-861. We propose that the
5-LOX pathway plays a crucial role in mitotic neurogenesis.
Additional studies should explore whether 5-LOX may participate
in neurogenesis related pathologies and whether it should be
considered a target for procedures aimed at altering neurogenesis
for therapeutic purposes.
