Molecular Targets of Angiogenesis and Future Potential of Anti-angiogensis Therapy in Multiple Sclerosis
Pp. 137-161 (25)
Manisha J. Oza, Sachin V. Suryavanshi, Mayuresh S. Garud, Sandip T. Auti, Ankit P. Laddha and Yogesh A. Kulkarni
Multiple sclerosis (MS) is a chronic, inflammatory, gray and white matter
demyelinating disease of the central nervous system characterized by axon
degeneration, oligodendrocytes damage and astrogliosis. As per epidemiological data
obtained from national multiple sclerosis society, 2.3 million people are suffering from
MS worldwide. In America and Europe, it is a leading cause of mortality in young
adults. The MS international federation reports showed that the prevalence of MS has
been increased up to 33/10000 in 2013 from 30/10000 in 2008. Along with degerative
processes, such as axon damage and myelin sheaths destruction, inflammatory
components, such as lymphocytes and macrophages also play pivotal role in the
pathogenesis of MS. There is an infiltration of immune cells, macrophages and
microglia, increased expression of cytokines and chemokines. The structural and
functional changes in Blood Brain Barrier occur very commonly in MS.
Angiogenesis is a process of development of new blood vessels from the existing blood
vessels. It is commonly involved in various CNS disorders, such as stroke, epilepsy and
tumors, indicating that it might have a role in the progression of MS lesions. The
inflammatory components involved in pathogenesis of MS have been observed to play
significant role to support angiogenesis. Inter cellular cell adhesion molecule-1
(ICAM-1), vascular endothelial growth factor (VEGF), vascular cell adhesion molecule
(VCAM) -1, matrix metalloproteinase -1, -2, -3, -7 and 9 (MMP-1,-2,-3,-7,-9), TNF-α
/-β, Interferon – γ (IFN– γ) and many other components are involved in angiogenesis
processes of MS. Moreover, MMPs and VEGF play significant role in vascular
basement membrane degradation and breakdown of BBB in MS. This indicates that
there is a firm link between angiogenesis and chronic inflammation for neovascularization
in the progression of MS. Since the inflammation and angiogenic processes are very complex and involve multiple biochemical processes, there are several molecular
targets associated with angiogenesis for therapeutic intervention in MS.
Thus, the aim of the present chapter will be to show the link between angiogenesis and
inflammatory processes in the progression of multiple sclerosis. Furthermore, the
chapter is also focused on the role of molecular targets of angiogenesis process in MS
along with their inhibitors or activators from various sources.
Angiogenesis, Blood brain barrier, Demyelination, Experimental
autoimmune encephalomyelitis, Hypoxia, Immune cells, Integrins, Interferon,
Matrix metalloproteinase, Minocycline, Multiple sclerosis, Quercetin, Vascular
endothelial growth factor.
Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM’s NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai-400056, India.