*1.2. VEGF Family*

Since the discovery of the first member of the VEGF family, known as VEGF-A, the family has continued to grow and is currently constituted by VEGF-A, VEGF-B [6,7], VEGF-C [8,9], VEGF-D [10,11], VEGF-E [12], VEGF-F [13] and placental growth factor (PlGF [14]).

VEGF-A stands out as the most studied VEGF family members because of its essential roles in neuroprotection. The gene encoding VEGF-A is located on chromosome 6p21.5, giving rise to three different isoforms (VEGF-A 121, VEGF-A 145, VEGF-A 165), which

A.M.; Morcuende, S. Neuroprotective Effect of Vascular Endothelial Growth Factor on Motoneurons of the Oculomotor System. *Int. J. Mol. Sci.* **2021**, *22*, 814. https://doi.org/ 10.3390/ijms22020814

**Citation:** Silva-Hucha, S.; Pastor,


Received: 10 December 2020 Accepted: 13 January 2021 Published: 15 January 2021

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are differentiated by their molecular weight, solubility, biological functions, binding affinities to the components of the extracellular matrix, and tyrosine kinase receptor subtypes (RTKs) [15]. Furthermore, VEGF 165 is the predominant isoform in the central nervous system (CNS), where it acts as a protection factor by promoting the survival of motoneurons [16,17]. This vital role is the one that interests us and the one that we will develop on throughout this review.

On the other hand, VEGF-B is also expressed in the CNS and can regulate adult neurogenesis and even rescuing neurons from apoptosis, but with less vascular effects and worse neuroprotective function on motoneurons than VEGF-A [18]. It has recently been discovered that the presence of VEGF-B is neither necessary nor essential for the survival, maintenance, and development of motoneurons under normal physiological conditions [19,20]. Finally, mention should be made of the members VEGF-C and VEGF-D, which regulate lymphatic angiogenesis, and of VEGF-E, which is virally encoded and specifically expressed in the venom of the habu snake (*Trimeresurus flavoviridis)* [21].
