Expression of collagen XVII and ubiquitin-binding protein p62 in motor neuron disease

• Published in: Brain research Vol. 1247; pp. 171 - 177
• Main Authors: Seppänen, Allan, Pikkarainen, Maria, Hartikainen, Päivi, Hofmann, Silke C., Majamaa, Kari, Alafuzoff, Irina
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 09.01.2009; Elsevier
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Adult; Aged; Aged, 80 and over; Amyotrophic Lateral Sclerosis - genetics; Amyotrophic Lateral Sclerosis - metabolism; Amyotrophic Lateral Sclerosis - physiopathology; Autoantigens - genetics; Autoantigens - metabolism; Biological and medical sciences; Biomarkers - analysis; Biomarkers - metabolism; Brain - metabolism; Brain - pathology; Brain - physiopathology; Cerebellum - metabolism; Cerebellum - pathology; Cerebellum - physiopathology; Cerebrospinal fluid. Meninges. Spinal cord; Collagen Type XVII; Collagen XVII; Comorbidity; Cytoskeleton - metabolism; Cytoskeleton - pathology; Dermatologi och venerologi, klinisk genetik, invärtesmedicin; Dermatology and venerology,clinical genetics, internal medicine; Female; Frontal Lobe - metabolism; Frontal Lobe - pathology; Frontal Lobe - physiopathology; Hippocampus - metabolism; Hippocampus - pathology; Hippocampus - physiopathology; Humans; Immunohistochemistry; Internal medicine; Invärtesmedicin; Male; Medical sciences; MEDICIN; MEDICINE; Middle Aged; Morfologi, cellbiologi, patologi; Morphology, cell biology, pathology; Motor neuron disease; Motor Neuron Disease - genetics; Motor Neuron Disease - metabolism; Motor Neuron Disease - physiopathology; Nervous system (semeiology, syndromes); Neurocognitive Disorders - metabolism; Neurocognitive Disorders - pathology; Neurocognitive Disorders - physiopathology; Neurologi; Neurology; Neurons - metabolism; Neurons - pathology; Non-Fibrillar Collagens - genetics; Non-Fibrillar Collagens - metabolism; p62; Pathology; Patologi; Sequestosome-1 Protein; coll XVII; MND; NCI; PMA; Collagen XVII; NT; TDP-43; Motor neuron disease; ALS; CNS; IR; p62; motor neuron disease; neuronal cytoplasmic inclusions; progressive muscular atrophy; amyotrophic lateral sclerosis; central nervous system; immunoreactive; trans-activating responsive sequence DNA-binding protein 43; neurites; ubiquitin-binding protein p62/sequestosome 1; collagen XVII, FTLD-U/ALS, frontotemporal lobar degeneration with ubiquitinated inclusions and amyotrophic lateral sclerosis, IHC, immunohistochemistry; Human; Ubiquitin; Nervous system diseases; Glycoprotein; Gene expression; Binding protein; Collagen; Central nervous system disease; Degenerative disease; Spinal cord disease
• ISSN: 0006-8993; 1872-6240; 1872-6240
• DOI: 10.1016/j.brainres.2008.10.020

Collagen involvement in motor neuron disease has been suggested by several earlier studies. Recently, we found collagen XVII to be expressed in locations in the human brain that include those damaged in motor neuron disease. In this study, we examined the extent of motor neuron disease-related changes in the brain of 9 subjects using ubiquitin-binding protein p62/sequestosome 1 (p62) immunohistochemistry. We then assessed whether or not the expression of collagen XVII was altered in relation to the p62 immunoreactive lesions. We found that neuronal collagen XVII expression in motor neuron disease remains similar to that seen in the normal human brain and thus a change in collagen XVII expression is not an immunohistochemically detectable feature of motor neuron disease. We also found that the regional distribution of p62 varied according to clinical presentation: p62 immunoreactive inclusions were found in the frontal cortex, hippocampus and cerebellum only in subjects with a history of psychiatric morbidity. Our study supports the re-definition of motor neuron disease as a multisystem disorder with a wide clinicopathological spectrum, and we advocate addressing psychiatric symptomology in future studies of motor neuron disease.