Abstract
Oxidative stress and angiogenic factors have been placed as the prime focus of scientific investigations after an establishment of link between vascular endothelial growth factor promoter (VEGF), hypoxia, and amyotrophic lateral sclerosis (ALS) pathogenesis. Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter and mutant superoxide dismutase 1 (SOD1) which are characterised by atrophy and muscle weakness resulted in phenotype resembling human ALS in mice. This results in lower motor neurodegeneration thus establishing an important link between motor neuron degeneration, vasculature, and angiogenic molecules. In this review, we have presented human, animal, and in vitro studies which suggest that molecules like VEGF have a therapeutic, diagnostic, and prognostic potential in ALS. Involvement of vascular growth factors and hypoxia response elements also highlights the converging role of oxidative stress and neurovascular network for understanding and treatment of various neurodegenerative disorders like ALS.
Highlights
At the developmental stages, the establishment of a neurovascular network, outside central nervous system (CNS), is crucial to the subsequent brain and spinal cord development
Abnormal expression and reduced levels of vascular endothelial growth factor promoter (VEGF) have been explored to account for devastating disorders of the CNS, especially in studies focused on amyotrophic lateral sclerosis (ALS), which is designated by motor neuron degeneration and is fatal in nature [5]
Genetic studies in a transgenic mouse and rat model of ALS with mutated superoxide dismutase 1 SOD1G93A have indicated that inhibition of hypoxia response element (HRE) in the VEGF gene promoter may promote motor neuron degeneration whereas administration of VEGF prolongs survival [6]
Summary
The establishment of a neurovascular network, outside CNS, is crucial to the subsequent brain and spinal cord development. Any dysregulation in the pathways having the above mentioned factors (responsible for angiogenesis) which contributes to the development of this communication network has serious consequences manifesting in the form of CNS disorders. Abnormal expression and reduced levels of VEGF have been explored to account for devastating disorders of the CNS, especially in studies focused on ALS, which is designated by motor neuron degeneration and is fatal in nature [5]. Genetic studies in a transgenic mouse and rat model of ALS with mutated superoxide dismutase 1 SOD1G93A have indicated that inhibition of hypoxia response element (HRE) in the VEGF gene promoter may promote motor neuron degeneration (since HRE is responsible for inducing angiogenesis through VEGF as shown in Figure 1) whereas administration of VEGF prolongs survival [6].
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