Researchers have found that bezafibrate, a lipid-lowering drug that inhibits the synthesis of VLCFA, can slow the loss of neurons and glia, two major types of brain cells. To understand how increased her VLCFA levels in glia affect lipid metabolism, they performed mass spectrometric analysis of 26 lipids obtained from adult fly heads lacking the fly version of d. rice field.ACOX1 gene. They found that two lipid intermediates – very long ceramide and sphingosine-1-phosphate (S1P) – were significantly higher in the glia of these flies.
Excess glial S1P, a VLCFA breakdown product, was transported to neurons. This increase was detrimental to glial cell and neuronal survival, causing dysfunction and degeneration of these cells.However, supplementing dCOX1 Mutant flies with fingolimod, an MS therapeutic, resulted in improved overall survival and neurological function and delayed neurodegeneration in these flies.
Researchers have also observed that flies lack dCOX1 There were several large black black masses all over the body, including the head, eyes, wing margins and abdomen. this is, dCOX1 It induces immune cells to attack their own cells.
they then dCOX1 Loss also activated other immune pathways. One of his two major immune pathways in flies, the immunodeficiency pathway, controls inducible immune responses against invading bacteria and fungi by producing cytokines and antimicrobial peptides upon activation of nuclear factor kB. help you to The researchers found that her S1P elevation in fly glia activates nuclear factor-kB and significantly increases the transcription levels of several antimicrobial peptide genes involved in immunodeficiency pathways.
Next, the team investigated the role of elevated VLCFA and S1P in MS-like pathology and MS progression in mice with induced immune responses. They found that presymptomatic treatment of these mice with bezafibrate reduced demyelination and neuronal damage. Administration of bezafibrate together with fingolimod at symptom onset synergistically ameliorated induced paralysis and motor performance, demyelination, and neuronal loss. The combined effects of these drugs were significantly superior to the effects of either drug alone. They concluded that concomitant use of bezafibrate and fingolimod ameliorated symptoms of induced multiple sclerosis in mice, suggesting that reduction of VLCFA and S1P may be a therapeutic tool for multiple sclerosis. suggesting.
“We are excited about the potential clinical implications of this study not only for how MS patients are treated, but also for other neurodegenerative conditions associated with demyelination, perturbed lipid metabolism, and neuroinflammation,” said co-authors. Baylor University Professor Hugo Bellen said in a statement.
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