Roles of Vascular Endothelial Growth Factor in Amyotrophic Lateral Sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal devastating neurodegenerative disorder, involving progressive degeneration of motor neurons in spinal cord, brainstem, and motor cortex. Riluzole is the only drug approved in ALS but it only confers a modest improvement in survival. In spite of a high number of clinical trials no other drug has proved effectiveness. Recent studies support that vascular endothelial growth factor (VEGF), originally described as a key angiogenic factor, also plays a key role in the nervous system, including neurogenesis, neuronal survival, neuronal migration, and axon guidance. VEGF has been used in exploratory clinical studies with promising results in ALS and other neurological disorders. Although VEGF is a very promising compound, translating the basic science breakthroughs into clinical practice is the major challenge ahead. VEGF-B, presenting a single safety profile, protects motor neurons from degeneration in ALS animal models and, therefore, it will be particularly interesting to test its effects in ALS patients. In the present paper the authors make a brief description of the molecular properties of VEGF and its receptors and review its different features and therapeutic potential in the nervous system/neurodegenerative disease, particularly in ALS.

Plasma derived from human umbilical cord blood: Potential cell‐additive or cell‐substitute therapeutic for neurodegenerative diseases

“…A recently published study demonstrated that microRNA‐containing exosomes derived from maternal and umbilical cord serum dramatically promote human umbilical vein endothelial cell proliferation, migration, and tube formation in vitro, highlighting the important role of exosomes in the regulation of angiogenesis during gestation. Exclusively, VEGF has been studied for potential therapeutic efficacy in animal models of ALS and its use in clinical settings has been discussed (reviewed). Nevertheless, CBP containing high levels of IL‐8 and VEGF might be a beneficial treatment for repair of the damaged blood–brain barrier and/or blood–spinal cord barrier in patients with ALS, AD, Parkinson's disease and multiple sclerosis …”

“…It is possible that the elevated level of VEGF is a result of the high concentration of IL-8, which promotes increased expression of VEGF by endothelial cells. 35,36 A recently published study 37 Exclusively, VEGF has been studied for potential therapeutic efficacy in animal models of ALS 38,39 and its use in clinical settings has been discussed (reviewed 40 ). Nevertheless, CBP containing high levels of EHRHART ET AL.…”

Profilin1 biology and its mutation, actin(g) in disease

“…Hence, it is likely that an interaction also occurs between profilin1 and the unmodified mDia . Profilin1 also interacts with vascular endothelial growth factor (VEGF), a small protein and a known neurotropic factor involved in angiogenesis, which also was implicated recently in cell signaling and tumorigenesis [23]. Specifically, VEGF-A binding to VEGF receptor 2 (VEGFR2) triggers phosphorylation of profilin1 Y129, increasing profilin1’s affinity for actin and thereby enhancing actin polymerization at the edge of the cell - the filopodium effect (Figure 1A).…”

Insights into the Mechanisms Involved in Protective Effects of VEGF-B in Dopaminergic Neurons

“…In one particular study, VEGF-A had promising results, with neuroprotection of motor neurons significantly improving neuronal survival in animal models [52]. However, as previously mentioned, the issues with VEGF-A's safety profile remain.…”