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Effects of signaling through the retinoic acid receptors in motor neurons: implications for amyotrophic lateral sclerosis
Author(s) -
Kolarcik Christi,
Bowser Robert
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.356.5
Subject(s) - amyotrophic lateral sclerosis , motor neuron , retinoic acid , neuroscience , receptor , neuron , biology , retinoic acid receptor , retinoid , medicine , cell culture , disease , biochemistry , genetics , spinal cord
Amyotrophic lateral sclerosis (ALS), the most common form of motor neuron disease, is a progressive, fatal neurodegenerative disorder which is poorly understood and for which effective therapeutic interventions are lacking. Our laboratory has identified potential biomarkers for ALS and has characterized these proteins and related signaling pathways using a primary motor neuron‐enriched cell culture system. We focused on retinoid signaling as we have observed alterations in this pathway in sporadic ALS patients. Using all‐trans retinoic acid (ATRA) to stimulate the retinoic acid receptors (RARs), we further investigated the impact of signaling through the RARs on motor neuron survival. In the presence of ATRA, the number of branch points/cell was decreased in motor neurons. RAR β was localized to the nucleus irrespective of the presence of ATRA. RARα localized to axonal processes without ATRA, and this decreased with increasing ATRA concentrations. As similar phenomena have been observed in sporadic ALS patients, we believe that motor neurons may attempt to recapitulate a developmental process in an effort to maintain axonal connections as ALS progresses. Research Support: NIH grant ES013469 (RB); NIH T32 EB001026 (CK); NIH T32 05 TL1 RR024155‐02 (CK)