Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Gene/Protein
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Target Concepts:
Gene/Protein
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Query: UMLS:C0016719 (
Friedreich's ataxia
)
2,098
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Friedreich's ataxia
(
FRDA
) is a neurodegenerative disorder caused by an unstable GAA repeat expansion within intron 1 of the FXN gene and characterized by peripheral neuropathy. A major feature of
FRDA
is frataxin deficiency with the loss of large sensory neurons of the dorsal root ganglia (DRG), namely proprioceptive neurons, undergoing dying-back neurodegeneration with progression to posterior columns of the spinal cord and cerebellar ataxia. We used isolated DRGs from a YG8R
FRDA
mouse model and C57BL/6J control mice for a proteomic study and a primary culture of sensory neurons from DRG to test novel pharmacological strategies. We found a decreased expression of electron transport chain (ETC) proteins, the oxidative phosphorylation (OXPHOS) system and antioxidant enzymes, confirming a clear impairment in mitochondrial function and an oxidative stress-prone phenotype. The proteomic profile also showed a decreased expression in Ca
2+
signaling related proteins and G protein-coupled receptors (GPCRs). These receptors modulate intracellular cAMP/cGMP and Ca
2+
levels. Treatment of frataxin-deficient sensory neurons with
phosphodiesterase
(
PDE
) inhibitors was able to restore improper cytosolic Ca
2+
levels and revert the axonal dystrophy found in DRG neurons of YG8R mice. In conclusion, the present study shows the effectiveness of
PDE
inhibitors against axonal degeneration of sensory neurons in YG8R mice. Our findings indicate that
PDE
inhibitors may become a future
FRDA
pharmacological treatment.
...
PMID:Phosphodiesterase Inhibitors Revert Axonal Dystrophy in Friedreich's Ataxia Mouse Model. 3076 10
