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Tytuł:
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Disease mechanism, biomarker and therapeutics for spinal and bulbar muscular atrophy (SBMA).
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Autorzy:
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Atsushi Hashizume
Fischbeck, Kenneth H.
Pennuto, Maria
Fratta, Pietro
Masahisa Katsuno
Hashizume, Atsushi
Katsuno, Masahisa
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Temat:
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SPINAL muscular atrophy
MEDICAL sciences
THERAPEUTICS
AMYOTROPHIC lateral sclerosis
MOTOR neuron diseases
CEREBELLUM degeneration
SPINOCEREBELLAR ataxia
SOMATOMEDIN
ADRENERGIC beta agonists
X-linked bulbo-spinal atrophy
LEUPROLIDE
SKELETAL muscle
DNA
MUSCLES
AUTOPHAGY
CELL receptors
MAGNETIC resonance imaging
NUCLEOTIDES
MITOCHONDRIA
CLENBUTEROL
ENZYME inhibitors
OXIDATION-reduction reaction
ADIPOSE tissues
CREATININE
GLYCOLYSIS
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Źródło:
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Journal of Neurology, Neurosurgery & Psychiatry; Oct2020, Vol. 91 Issue 10, p1085-1091, 7p
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Spinal and bulbar muscular atrophy (SBMA) is a hereditary neuromuscular disorder caused by CAG trinucleotide expansion in the gene encoding the androgen receptor (AR). In the central nervous system, lower motor neurons are selectively affected, whereas pathology of patients and animal models also indicates involvement of skeletal muscle including loss of fast-twitch type 2 fibres and increased slow-twitch type 1 fibres, together with a glycolytic-to-oxidative metabolic switch. Evaluation of muscle and fat using MRI, in addition to biochemical indices such as serum creatinine level, are promising biomarkers to track the disease progression. The serum level of creatinine starts to decrease before the onset of muscle weakness, followed by the emergence of hand tremor, a prodromal sign of the disease. Androgen-dependent nuclear accumulation of the polyglutamine-expanded AR is an essential step in the pathogenesis, providing therapeutic opportunities via hormonal manipulation and gene silencing with antisense oligonucleotides. Animal studies also suggest that hyperactivation of Src, alteration of autophagy and a mitochondrial deficit underlie the neuromuscular degeneration in SBMA and provide alternative therapeutic targets. [ABSTRACT FROM AUTHOR]
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