Reviewing the Significance of Blood–Brain Barrier Disruption in Multiple Sclerosis Pathology and Treatment
| Autor: | Oana Mosora, Laura Barcutean, Rodica Balasa, Doina Manu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Multiple Sclerosis QH301-705.5 Sphingosine-1-phosphate receptor Review Blood–brain barrier Neuroprotection Catalysis Inorganic Chemistry 03 medical and health sciences 0302 clinical medicine Immune system medicine Animals Humans Biology (General) Physical and Theoretical Chemistry Cladribine QD1-999 Molecular Biology Spectroscopy disease modifying therapies progression impermeability business.industry Multiple sclerosis Organic Chemistry Neurodegeneration Endothelial Cells General Medicine Hypoxia (medical) medicine.disease Mitochondria Computer Science Applications Chemistry 030104 developmental biology medicine.anatomical_structure Blood-Brain Barrier Disease Progression medicine.symptom business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 8370, p 8370 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22168370 |
| Popis: | The disruption of blood–brain barrier (BBB) for multiple sclerosis (MS) pathogenesis has a double effect: early on during the onset of the immune attack and later for the CNS self-sustained ‘inside-out’ demyelination and neurodegeneration processes. This review presents the characteristics of BBB malfunction in MS but mostly highlights current developments regarding the impairment of the neurovascular unit (NVU) and the metabolic and mitochondrial dysfunctions of the BBB’s endothelial cells. The hypoxic hypothesis is largely studied and agreed upon recently in the pathologic processes in MS. Hypoxia in MS might be produced per se by the NVU malfunction or secondary to mitochondria dysfunction. We present three different but related terms that denominate the ongoing neurodegenerative process in progressive forms of MS that are indirectly related to BBB disruption: progression independent of relapses, no evidence of disease activity and smoldering demyelination or silent progression. Dimethyl fumarate (DMF), modulators of S1P receptor, cladribine and laquinimode are DMTs that are able to cross the BBB and exhibit beneficial direct effects in the CNS with very different mechanisms of action, providing hope that a combined therapy might be effective in treating MS. Detailed mechanisms of action of these DMTs are described and also illustrated in dedicated images. With increasing knowledge about the involvement of BBB in MS pathology, BBB might become a therapeutic target in MS not only to make it impenetrable against activated immune cells but also to allow molecules that have a neuroprotective effect in reaching the cell target inside the CNS. |
| Databáze: | OpenAIRE |
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