VEGF-B as a therapeutic intervention for Parkinson's disease

Since it was discovered that the brain had tremendous neuroregenerative potential, growth factors have been highly speculated as therapeutic tools.  The vascular endothilial growth factor (VEGF) family, and particularly VEGF-B, has recently been distinguished as having a neuroprotective role in the Parkinsonian brain.

Carolina Hagberg et al. published the findings in Nature Letters earlier this year that VEGF-B was tightly co-expressed with several mitochondrial genes, suggesting a role for this growth factor in metabolism.  VEGF-B was specifically found to regulate endothilial fatty acid transport (uptake) proteins, and thus, the uptake of fatty acids into peripheral and heart muscle, and brown adipose tissue.  The co-expression of VEGF-B and mitochondrial proteins suggests a coordination of endothilial lipid uptake and mitochondrial lipid use, which is why it is an attractive intervention for PD, wherein it is thought that dopaminergic neurons die by dysfunction of mitochondrial metabolism.

This mechanistic information provides support for work lead by Torsten Falk at the University of Arizona suggesting a role for VEGF-B in the Parkinsonian brain.  In a 2009 study, a midbrain cell culture showed upregulation of the VEGF-B gene following treatment with rotenone (a pesticide specifically toxic to dopaminergic neurons, and commonly used in non-primate animal models of PD).  Additionally, application of exogenous VEGF-B to cell cultures resulted in neuroprotection from rotenone toxicity.

More recently, Falk et al. have shown exogenous VEGF-B to be neuroprotective in vivo.  From a 2006 study by Sun et al., intraventricularly administered VEGF-B restored neurogenesis to wild-type levels in VEGF-B knockout mice.

In corroboration with the Hagberg study, there is a strong suggestion that VEGF-B may be neuroregenerative via direct effect on mitochondrial function.  Correlative studies associating VEGF-B expression with midbrain mitochondrial un-coupling proteins, Complex I, or apoptotic cascades remain to be seen.  Additionally, there are no reports of VEGF-B's capacity to be neurorestorative, or slow dopaminergic neurodegeneration in a progressive PD model.


Hagberg, C., Falkevall, A., Wang, X., Larsson, E., Huusko, J., Nilsson, I., van Meeteren, L., Samen, E., Lu, L., Vanwildemeersch, M., Klar, J., Genove, G., Pietras, K., Stone-Elander, S., Claesson-Welsh, L., Ylä-Herttuala, S., Lindahl, P., & Eriksson, U. (2010). Vascular endothelial growth factor B controls endothelial fatty acid uptake Nature, 464 (7290), 917-921 DOI: 10.1038/nature08945

T. A. FALK, X. YUE, S. ZHANG, S. J. SHERMAN (2010). Evidence for neuroprotection after treatment with Vascular Endothelial Growth Factor-B in vivo in the 6-hydroxydopamine rat model of Parkinson’s disease Society for Neuroscience 2010 Abst.

Sun, Y., Jin, K., Childs, J., Xie, L., Mao, X., & Greenberg, D. (2006). Vascular endothelial growth factor-B (VEGFB) stimulates neurogenesis: Evidence from knockout mice and growth factor administration Developmental Biology, 289 (2), 329-335 DOI: 10.1016/j.ydbio.2005.10.016