Abstract
IntroductionChromosome 9 open reading frame 72 (C9orf72) is an evolutionarily conserved protein with unknown function, expressed at high levels in the brain. An expanded hexanucleotide GGGGCC repeat located in the first intron of the C9orf72 gene represents the most common genetic cause of familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Previous studies by immunohistochemistry with two different anti-C9orf72 antibodies named sc-138763 and HPA023873 showed that C9orf72 is expressed chiefly in the cytoplasm of neurons, and is concentrated in the synaptic terminals in the brains of FTD/ALS with or without C9orf72 repeat expansion as well as those of controls. At present, a pathological role of C9orf72 in the process of neurodegeneration remains unknown.MethodsUsing immunohistochemistry we studied C9orf72 expression in the frontal cortex and the hippocampus of six Alzheimer's disease (AD) and 13 control cases, including ALS, Parkinson's disease, multiple system atrophy, and non-neurological cases.ResultsThe HPA023873 antibody showed a cross-reactivity to glial fibrillary acidic protein, and therefore stained intensely reactive astrocytes in AD and non-AD brains. Both sc-138763 and HPA023873 antibodies labeled the neuronal cytoplasm and the neuropil with variable intensities, and intensely stained a cluster of p62-negative, UBQLN1-positive swollen neurites, which were distributed in the CA1 region and the molecular layer in the hippocampus of both AD and non-AD brains. Most notably, both of these antibodies reacted strongly with dystrophic neurites accumulated on senile plaques in AD brains.ConclusionThese results suggest a general role of C9orf72 in the process of neurodegeneration in a range of human neurodegenerative diseases.
Highlights
Chromosome 9 open reading frame 72 (C9orf72) is an evolutionarily conserved protein with unknown function, expressed at high levels in the brain
These results suggest a general role of C9orf72 in the process of neurodegeneration in a range of human neurodegenerative diseases
Recent studies indicate that an expanded hexanucleotide GGGGCC repeat located in the first intron of the C9orf72 gene represents the most common genetic abnormality for familial cases of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) with European ancestry, both of which constitute an overlapping continuum of a multisystem disorder affecting the central nervous system (CNS) [1,2,3,4]
Summary
Chromosome 9 open reading frame 72 (C9orf72) is an evolutionarily conserved protein with unknown function, expressed at high levels in the brain. An expanded hexanucleotide GGGGCC repeat located in the first intron of the C9orf gene represents the most common genetic cause of familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Chromosome 9 open reading frame 72 (C9orf72) is an evolutionarily conserved protein with unknown function, expressed in most tissues including the brain. Recent studies indicate that an expanded hexanucleotide GGGGCC repeat located in the first intron of the C9orf gene represents the most common genetic abnormality for familial cases of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) with European ancestry, both of which constitute an overlapping continuum of a multisystem disorder affecting the central nervous system (CNS) [1,2,3,4]. A panel of missense mutations is identified in the gene encoding p62, known as sequestosome 1, in familial and sporadic ALS patients, supporting a key role for p62 in the pathogenesis of FTD/ALS [21]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
