Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mRNA levels of RET and GDNFR-alpha were studied in the spinal cord of patients with amyotrophic lateral sclerosis (ALS) by reverse transcription followed by polymerase chain reaction (RT-PCR) and in situ hybridization (ISH). Semiquantitative RT-PCR analysis revealed that RET mRNA levels in the ALS spinal cord anterior horn were reduced to one fifth of controls in proportion to motor neuron loss, whereas GDNFR-alpha mRNA was unchanged. ISH analysis showed that RET mRNA was expressed in the anterior horn motor neurons of the spinal cord, but GDNFR-alpha mRNA was expressed widely in the spinal cord neurons and glial cells. The RET mRNA levels, measured using a CCD image analyzer, were substantially preserved in individual motor neurons of ALS, but varied among those neurons. Relatively high levels of RET mRNA were observed in a certain population of atrophic neurons. On the other hand, the GDNFR-alpha mRNA levels in the motor neurons were similar in ALS and controls. In addition, the RET protein was also well expressed in individual motor neurons in ALS. These results indicate that GDNF receptor expression persists at mRNA and protein levels in the degenerating motor neurons in ALS, supporting the view that GDNF is a candidate for therapeutic approach to ALS.
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PMID:Expression of GDNF receptor (RET and GDNFR-alpha) mRNAs in the spinal cord of patients with amyotrophic lateral sclerosis. 1002 33

Gorelenkova Miller and Mieyal (Arch Toxicol 89(9): 1439-1467, 2015) recently published a review paper suggesting that reversible cysteine plays a key role in redox-linked signal transduction via alteration of protein function, resulting in an association with many diseases including neurodegenerative disorders. Following their suggestions, we considered the correlation between sulfhydryl-mediated redox signaling and neurodegenerative diseases by focusing on RET proteins, a protein tyrosine kinases (PTKs) potentially sited upstream of the signal transduction cascade. c-RET is the receptor for glial cell line-derived neurotrophic factor family ligands. c-RET has been reported to be involved in not only Hirschsprung disease via development of the enteric nervous system but also neurodegenerative diseases including Parkinson's disease and amyotrophic lateral sclerosis. We also showed that c-RET might be associated with hearing loss via neurodegeneration of spiral ganglion neurons in the inner ear after birth in mice and humans. Moreover, we have reported that three kinds of oxidative stress, ultraviolet light-induced stress, osmotic stress and arsenic-induced stress, modulate kinase activity of RET-PTC1 without an extracellular domain as well as c-RET by conformational change of RET protein (dimerization) via disulfide bond formation. The oxidative stresses also modulate kinase activity of RET-PTC1 with cysteine 365 (C365) replaced by alanine with promotion of dimer formation, but not with cysteine 376 (C376) replaced by alanine. Since C376 of Ret-PTC-1 or its equivalent is most highly conserved and crucial for activity in PTKs, the cysteine could be one of major targets for oxidative stresses.
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PMID:Commentary to Gorelenkova Miller and Mieyal (2015): sulfhydryl-mediated redox signaling in inflammation: role in neurodegenerative diseases. 2693 17