Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Target Concepts:
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Query: UMLS:C0002736 (
amyotrophic lateral sclerosis
)
19,048
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Metabolic dysfunction is a hallmark of age-related neurodegenerative diseases, including
amyotrophic lateral sclerosis
(
ALS
). But the crosstalk between metabolic alteration and disease progression in
ALS
is still largely unknown. Glycogen, a branched polymer of glucose residues, is universally recognized as the energy reserve of the central nervous system (CNS), where its aberrant accumulation instigates neurodegeneration. Glycogen was reported to be accumulated in both CNS and visceral organs of SOD1
G93A
mice, a well-known
ALS
model, and contributes to the pathological process of
ALS
. However, the accumulative patterns and mechanisms are not well elucidated. Here, we provide extensive evidence to demonstrate that glycogen accumulated in the lumbar spinal cord of
ALS
mice along with the disease progression, but not in the motor cortex. This regional accumulation of glycogen was caused by deteriorated glycogenolysis, which was triggered by decreased glycogen phosphorylase, brain form (
PYGB
). Moreover,
miR-338-3p
, an elevated miRNA in the spinal cord of SOD1
G93A
mice, directly targeted
PYGB
and was responsible for the decreased glycogenolysis and subsequent glycogen accumulation. Our work is helpful for better understanding of of of metabolic dysfunctions in
ALS
and provides novel targets for the therapeutic intervention in the future.
...
PMID:Decreased Glycogenolysis by
miR-338-3p
Promotes Regional Glycogen Accumulation Within the Spinal Cord of Amyotrophic Lateral Sclerosis Mice. 3113 99
