title: Loss of hnRNPA1 in ALS spinal cord motor neurons with TDP-43-positive inclusions.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of motor neurons and appearance of skein-like inclusions. The inclusions are composed of trans-activation response (TAR) DNA-binding protein 43 (TDP-43), a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family. hnRNPA1 and hnRNPA2/B1 are hnRNPs that interact with the C-terminus of TDP-43. Using immunohistochemistry, we investigated the association between TDP-43 and hnRNPA1 in ALS spinal motor neurons. We examined spinal cords of seven ALS cases and six muscular dystrophy cases (used as controls) for the presence of TDP-43 and hnRNPA1 protein. In the control cases, hnRNPA1 immunoreactivity in motor neurons was intense in the nucleus and weak in the cytoplasm where it showed a fine granular appearance. In the ALS cases, hnRNPA1 immunoreactivity in motor neurons was reduced in the nuclei of neurons with skein-like inclusions but was not detected in the skein-like inclusions. The marked loss of hnRNPA1 in motor neurons with concomitant cytoplasmic aggregation of TDP-43 may represent a severe disturbance of mRNA processing, suggesting a key role in progressive neuronal death in ALS.
authors.affiliation: Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Honda
authors.forename: Hideomi
authors.initials: H
authors.lastname: Hamasaki
authors.forename: Tomihiro
authors.initials: T
authors.lastname: Wakamiya
authors.forename: Sachiko
authors.initials: S
authors.lastname: Koyama
authors.forename: Satoshi O
authors.initials: SO
authors.lastname: Suzuki
authors.forename: Naoki
authors.initials: N
authors.lastname: Fujii
authors.forename: Toru
authors.initials: T
authors.lastname: Iwaki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000378:metabolism*; D009136:Muscular Dystrophies / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; C000598624:TARDBP protein, human; C000619656:hnRNPA1 protein, human
keywords: TDP-43; amyotrophic lateral sclerosis; hnRNP; hnRNPA1; motor neuron