Abstract
Multiple sclerosis (MS) is a neurodegenerative disease characterized by inflammation and myelin damage. Pro-inflammatory cytokines, oxidative stress, high level of matrix metalloproteinases (MMPs) activity and blood–brain barrier (BBB) damage, immune-mediated destruction of myelin and neuron loss are involved in the pathogenesis of MS. The currently approved treatments for MS include injectable drugs (interferon-β and glatiramer acetate), oral drugs (fingolimod), and monoclonal antibodies (natalizumab). The mentioned therapeutic choices are mostly focused on the inhibition of inflammation. Therefore, the search for a multi-target therapeutic choice remains unchallenged. It seems that a drug with anti-inflammatory, oxidative stress inhibitory, reduction of MMPs activity, and neurogenesis stimulatory properties may be effective for treatment of MS. In this regard, Bryostatin-1 as a macrolide and marine natural product has been selected as a therapeutic choice. Studies indicate that Bryostatin-1 has anti-inflammatory and antioxidant properties and decreases MMPs level and BBB damage. Furthermore, Bryostatin-1 has a neuroprotective effect and promotes neurogenesis and differentiation of oligodendrocyte progenitor stem cells as a critical step for remyelination/myelogenesis. Based on these properties, we hypothesized here that Bryostatin-1 is an effective treatment in MS.
Highlights
Multiple sclerosis (MS) is a neurodegenerative disease, characterized by inflammation and demyelination
The protection of neurons from possible damage and inducing neurogenesis and myelogenesis in the CNS are therapeutic targets which overcome the MS challenges. It seems that a drug with anti-inflammatory, oxidative stress inhibitory, matrix metalloproteinases (MMPs) inhibitory, and neurogenesis stimulatory properties may be effective for the treatment of MS
In Vitro Studies To evaluate the neuroprotective and anti-oxidant properties of Bryostatin-1, oligodendrocyte cell line such as the OLN-93 will be cultured and oxidative stress and cell death will be induced by H2O2 or cuprizone
Summary
Multiple sclerosis (MS) is a neurodegenerative disease, characterized by inflammation and demyelination. The protection of neurons from possible damage and inducing neurogenesis and myelogenesis in the CNS are therapeutic targets which overcome the MS challenges It seems that a drug with anti-inflammatory, oxidative stress inhibitory, MMPs inhibitory, and neurogenesis stimulatory properties may be effective for the treatment of MS. Shang et al (2016) studied the anti-oxidant effect of Bryostatin-1 Their results revealed that pre-treatment of cultured cells with Bryostatin-1 inhibit H2O2 induced cell death. MMPs cause damage to the brain in MS through two mechanisms: first, MMPs produced by leukocytes degrade vessel endothelial lining and result in BBB breakdown and the entrance of inflammatory cells to CNS. It has been reported that Bryostatin-1 reduces the hemorrhagic transformation following ischemic/reperfusion injuries and improves BBB disruption by down-regulation of MMP-9 expression and activation (Tan et al, 2015). We hypothesize here that Bryostatin-1 could be used to treat MS due to its antiinflammatory, anti-oxidant, neuroprotective, neurogenesis, and inhibition of metalloproteinase matrix properties (Figure 1)
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