Myelin plays a critical role in nervous system function and alterations in myelin-specific proteins cause a variety of neurologic disorders. We isolated a novel cDNA from the CNS that shares little nucleotide sequence homology with previously reported genes but appears to encode a protein related to peripheral myelin protein-22 (PMP-22) based on its amino acid sequence, predicted structure, and cellular localization. PMP-22 is important in peripheral myelination and Schwann cell proliferation, and mutations in its gene cause diseases of peripheral nerves. The isolated cDNA is 1.8 kb in length with an open reading frame of 621 bp. Northern blot analysis detected hybridization of labeled cDNA with a single 2.1-kb transcript only in the CNS. In situ hybridization revealed expression of this cDNA in oligodendrocytes of brain and spinal cord as well as in oligodendrocyte-enriched cultures; therefore we have named it oligodendrocyte-specific protein (OSP) cDNA. An OSP-specific polyclonal antibody reacted with a single 22-kd protein present in CNS myelin and oligodendrocytes. Developmental expression of OSP mRNA in the spinal cord was similar to that of the mRNA for a major myelin protein, proteolipid protein (PLP), and similar to PMP-22 in peripheral nerves. Since OSP is localized to oligodendrocytes and myelin, has a similar structure with PMP-22, and has a developmental pattern of expression like other myelin proteins, it probably has an important role in CNS myelinogenesis.
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http://dx.doi.org/10.1212/wnl.47.3.772 | DOI Listing |
J Zhejiang Univ Sci B
September 2024
Center for Rehabilitation Medicine, Department of Neurosurgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou 310014, China.
Acta Neuropathol Commun
November 2024
Department of Neuroscience and Pathobiology, Research Institute of Environmental Medicine, Nagoya University, Chikusa-Ku, Nagoya, Aichi, 464-8601, Japan.
Nuclear clearance and cytoplasmic aggregation of TAR DNA-binding protein of 43 kDa (TDP-43) are pathological hallmarks of amyotrophic lateral sclerosis (ALS) and its pathogenic mechanism is mediated by both loss-of-function and gain-of-toxicity of TDP-43. However, the role of TDP-43 gain-of-toxicity in oligodendrocytes remains unclear. To investigate the impact of excess TDP-43 on oligodendrocytes, we established transgenic mice overexpressing the ALS-linked mutant TDP-43 in oligodendrocytes through crossbreeding with Mbp-Cre mice.
View Article and Find Full Text PDFHeliyon
November 2024
Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
CDKL5 deficiency disorder (CDD) is a rare neurodevelopmental syndrome caused by mutations in the X-linked CDKL5 gene. Hundreds of pathogenic variants have been described, associated with a significant phenotypic heterogeneity observed among patients. To date, different knockout mouse models have been generated.
View Article and Find Full Text PDFMol Neurodegener
November 2024
Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT, 06030-3401, USA.
Background: The accumulation of β-amyloid (Aβ) peptides into insoluble plaques is an early pathological feature of Alzheimer's disease (AD). BACE1 is the sole β-secretase for Aβ generation, making it an attractive therapeutic target for AD therapy. While BACE1 inhibitors have been shown to reduce Aβ levels in people with AD, clinical trials targeting BACE1 have failed due to unwanted synaptic deficits.
View Article and Find Full Text PDFMol Ther Methods Clin Dev
December 2024
Department of Neurophysiology & Neural Repair, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
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