Role of Ca2+-Mediated signaling in als pathology

Ekaterina A. Kotelnikova, Mikhail A. Pyatnitskiy, R. L. Redler Rachel L., Nikolay Dokholyan

Research output: Chapter in Book/Report/Conference proceedingChapter


Familial amyotrophic lateral sclerosis (fALS) is a hereditary disorder of motor neurons that is caused by mutation in Cu, Zn superoxide dismutase (SOD1) in a subset of cases. The onset of the disease is relatively late, usually at age 50 or later, and is associated with interrelated molecular mechanisms of neurodegeneration. One of the mechanisms that can promote ALS progression is increased intracellular calcium concentration. The only market-available drug for ALS targets glutamate receptors and slows disease in part by mitigating excitotoxicity, a process in which persistent stimulation of glutamate receptors leads to pathologically high calcium concentration. To dissect the potential contributions of calcium mishandling to ALS, we have processed several publically available expression datasets related to fALS and analyzed the differential expression of genes related to calcium homeostasis. We find that SOD1- related fALS is associated with changes in expression of numerous genes related to calcium handling. Several genes which are down-regulated in fALS are targets of the repressor element-1 transcription factor/neuron restrictive silencer factor (REST/NRSF) transcription factor, which is normally inactivated in neuronal tissue. Our meta-analysis shows that changes in gene expression occurring in SOD1-related fALS promote calcium mishandling through dysregulation of multiple pathways, and that aberrant REST/NRSF activity may underlie some errors in calcium homeostasis.

Original languageEnglish (US)
Title of host publicationFrom Knowledge Networks to Biological Models
PublisherBentham Science Publishers Ltd.
Number of pages49
ISBN (Print)9781608054367
StatePublished - Dec 1 2012

All Science Journal Classification (ASJC) codes

  • Computer Science(all)
  • Biochemistry, Genetics and Molecular Biology(all)


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