methylmalonic acidemia

Human Anatomy & Physiology (11th Edition)
11th Edition
ISBN:9780134580999
Author:Elaine N. Marieb, Katja N. Hoehn
Publisher:Elaine N. Marieb, Katja N. Hoehn
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Reference: MicroRNA-9 regulates neural apoptosis in methylmalonic acidemia via targeting BCL2L11

Abstract
Methylmalonic acidemia (MMA) is an autosomal-recessive
inborn metabolic disorder that results from a deficiency in
methylmalonyl-coenzyme A mutase or its cofactor,
adenosylcobalamin. Currently, neurological manifestations in
MMA are thought to be associated with neural apoptosis.
BCL2L11, which is a proapoptotic Bcl-2 family member, is
resident in the outer mitochondrial membrane, where this
protein acts as a central regulator of the intrinsic apoptotic
cascade and mediates excitotoxic apoptosis. MicroRNAs
(miRNAs) are a class of non-coding RNAS that function as
endogenous triggers of the RNA interference pathway.
Currently, little is known regarding the role of miRNA in
MMA. In our previous study, we preliminarily found that the
expression of miR-9 was significantly down-regulated in
MMA patient plasma and sensitively changed after VitB12
treatment, which may act as a potential "competitor" of
chromatography-mass spectrometry for the diagnosis of
MMA. In the present study, we first confirmed that miR-9
inhibited BCL2L11 expression by directly targeting its 3'-
gas
untranslated region, and the up-regulation of miR-9 reduced
neural apoptosis induced by methylmalonate via targeting
BCL2L11. Taken together, our results suggested that miR-9
might act as a monitor of changes in MMA and might
provide new insights into a therapeutic entry point for
treating MMA.
Transcribed Image Text:Abstract Methylmalonic acidemia (MMA) is an autosomal-recessive inborn metabolic disorder that results from a deficiency in methylmalonyl-coenzyme A mutase or its cofactor, adenosylcobalamin. Currently, neurological manifestations in MMA are thought to be associated with neural apoptosis. BCL2L11, which is a proapoptotic Bcl-2 family member, is resident in the outer mitochondrial membrane, where this protein acts as a central regulator of the intrinsic apoptotic cascade and mediates excitotoxic apoptosis. MicroRNAs (miRNAs) are a class of non-coding RNAS that function as endogenous triggers of the RNA interference pathway. Currently, little is known regarding the role of miRNA in MMA. In our previous study, we preliminarily found that the expression of miR-9 was significantly down-regulated in MMA patient plasma and sensitively changed after VitB12 treatment, which may act as a potential "competitor" of chromatography-mass spectrometry for the diagnosis of MMA. In the present study, we first confirmed that miR-9 inhibited BCL2L11 expression by directly targeting its 3'- gas untranslated region, and the up-regulation of miR-9 reduced neural apoptosis induced by methylmalonate via targeting BCL2L11. Taken together, our results suggested that miR-9 might act as a monitor of changes in MMA and might provide new insights into a therapeutic entry point for treating MMA.
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