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Retinoid signaling pathway protein alterations in patients with 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.356.6
Subject(s) - amyotrophic lateral sclerosis , retinoid , retinoic acid , immunostaining , biology , signal transduction , spinal cord , cancer research , microbiology and biotechnology , immunohistochemistry , pathology , medicine , immunology , neuroscience , gene , genetics , disease
The mechanisms underlying the motor neuron (MN) degeneration that occurs with amyotrophic lateral sclerosis (ALS) are poorly understood. Multiple studies have described the differential expression of retinoid signaling components in ALS patients and transgenic animal models. We investigated this pathway in human lumbar spinal cord tissue of patients with sporadic (SALS) and familial (FALS) ALS as well as controls with immunohistochemistry, immunoblotting, co‐immunoprecipitation and DNA‐binding assays. In SALS MNs, cellular retinoic acid binding protein (CRABP)‐II, the protein responsible for facilitating nuclear receptor interactions, was concentrated to the nucleus while FALS and control MNs had a diffuse cytoplasmic pattern. Nuclear retinoic acid receptor (RAR) βexhibited increased immunoreactivity in MN nuclei of individuals with SALS although both controls and individuals with FALS lacked this nuclear immunostaining. For MNs with RARβ nuclear staining, activated caspase‐3 was negative. Our results indicate that retinoid signaling is altered in ALS. Differences with respect to RARβ suggest that retinoid signaling impacts only SALS and that this is a pro‐survival response. Research Support: NIH grant ES013469 (RB); NIH T32 EB001026 (CK); NIH T32 05 TL1 RR024155‐02 (CK)