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Detoxification of Reactive Aldehydes by Alda-1 Treatment Ameliorates Experimental Autoimmune Encephalomyelitis in Mice.
- Source :
-
Neuroscience . Mar2021, Vol. 458, p31-42. 12p. - Publication Year :
- 2021
-
Abstract
- • EAE results in the accumulation of reactive aldehydes in the CNS. • ALDH2 detoxifies reactive aldehydes in the mitochondria. • Alda-1, an agonist of ALDH2, reduces reactive aldehydes in the CNS of EAE animals. • Alda-1 treatment protects mitochondria and peroxisomes in the CNS of EAE animals. • Alda-1 treatment protects myelin and improves clinical outcome of EAE animals. Reactive aldehydes are generated as a toxic end-product of lipid peroxidation under inflammatory oxidative stress condition which is a well-established phenomenon in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Alda-1, a selective agonist of mitochondrial aldehyde dehydrogenase 2 (ALDH2), is known to detoxify the reactive aldehydes. In this study, we investigated the effect of Alda-1 on CNS myelin pathology associated with reactive aldehydes and mitochondrial/peroxisomal dysfunctions in a mouse model of EAE. Daily treatment of EAE mice with Alda-1, starting at the peak of disease, ameliorated the clinical manifestation of disease along with the improvement of motor functions. Accordingly, Alda-1 treatment improved demyelination and neuroaxonal degeneration in EAE mice. EAE mice had increased levels of reactive aldehyde species, such as 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), and acrolein (ACL) in the spinal cords and these levels were significantly reduced in Alda-1-treated EAE mice. Furthermore, Alda-1 treatment improved the loss of mitochondrial (OXPHOS) and peroxisomal (PMP70 and catalase) proteins as well as mitochondrial/peroxisomal proliferation factors (PGC-1α and PPARs) in the spinal cords of EAE mice. Taken together, this study demonstrates the therapeutic efficacy of ALDH2-agonist Alda-1 in the abatement of EAE disease through the detoxification of reactive aldehydes, thus suggesting Alda-1 as a potential therapeutic intervention for MS. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03064522
- Volume :
- 458
- Database :
- Academic Search Index
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 148985420
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2021.01.021