The potential of GPNMB as novel neuroprotective factor in amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is an incurable and fatal neurodegenerative disease characterized by the loss of motor neurons. Despite substantial research, the causes of ALS remain unclear. Glycoprotein nonmetastatic melanoma protein B (GPNMB) was identified as an ALS-related factor using DNA microarray analysis with mutant superoxide dismutase (SOD1(G93A)) mice. GPNMB was greatly induced in the spinal cords of ALS patients and a mouse model as the disease progressed. It was especially expressed in motor neurons and astrocytes. In an NSC34 cell line, glycosylation of GPNMB was inhibited by interaction with SOD1(G93A), increasing motor neuron vulnerability, whereas extracellular fragments of GPNMB secreted from activated astrocytes attenuated the neurotoxicity of SOD1(G93A) in neural cells. Furthermore, GPNMB expression was substantial in the sera of sporadic ALS patients than that of other diseased patients. This study suggests that GPNMB can be a target for therapeutic intervention for suppressing motor neuron degeneration in ALS.
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
Hirotaka
H
Tanaka
Masamitsu
M
Shimazawa
Masataka
M
Kimura
Masafumi
M
Takata
Kazuhiro
K
Tsuruma
Mitsunori
M
Yamada
Hitoshi
H
Takahashi
Isao
I
Hozumi
Jun-ichi
J
Niwa
Yohei
Y
Iguchi
Takeshi
T
Nikawa
Gen
G
Sobue
Takashi
T
Inuzuka
Hideaki
H
Hara
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D000818:Animals; D016923:Cell Death / Q000235:genetics; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009046:Motor Neurons / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D034622:RNA Interference; D013116:Spinal Cord / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
D005136:Eye Proteins; C445671:Gpnmb protein, mouse; D008562:Membrane Glycoproteins; D013482:Superoxide Dismutase