Immunoreactivity of myelin‐associated oligodendrocytic basic protein in Lewy bodies

Abstract

Myelin‐associated oligodendrocytic basic protein (MOBP) plays a role in structural maintenance of the myelin sheath in the central nervous system. Recent genome analyses have revealed that mutation in MOBP is a risk factor for various neurodegenerative diseases, including Alzheimer's disease (AD), tauopathies and transactivation response DNA‐binding protein 43 kDa proteinopathies. Proteomics analysis has shown that MOBP is a component of cortical Lewy bodies (LBs). However, the immunohistochemical localization of MOBP in the human brain is not known. Using immunohistochemistry, we examined the brain, spinal cord and peripheral ganglia from patients with various neurodegenerative diseases and control subjects. In normal controls, MOBP immunoreactivity was evident in the myelin in the central and peripheral nervous systems (PNS), and neuronal cytoplasm in both the central and PNS. In Parkinson's disease and dementia with LBs, MOBP immunoreactivity was found in the core of LBs in the brainstem, cingulate cortex and sympathetic ganglia. No MOBP immunoreactivity was found in a variety of other neuronal or glial inclusions in other disorders, including multiple system atrophy, AD, Pick's disease, progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease, amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Considering that up‐regulation of MOBP has been reported in neurotoxic conditions, accumulation of MOBP in LBs may imply a cytoprotective mechanism in LB disease.

MOBP and HIP1 in multiple system atrophy: New α‐synuclein partners in glial cytoplasmic inclusions implicated in the disease pathogenesis

“…Furthermore, we found strong immunopositive staining for MOBP in MSA cerebellar GCIs but not in midbrain PD Lewy bodies, nor in frontal cortex PSP or HD inclusions. Our findings contrast with results from a recent study by Kon et al, 47 who reported negative immunoreactivity for MOBP in cerebellar MSA GCIs, but positive immunoreactivity for MOBP in a proportion of Lewy bodies in PD and dementia with Lewy bodies cases. Technical differences between these two studies may contribute to the observed discrepancy in the immunostaining.…”

Myelin‐associated oligodendrocyte basic protein rs616147 polymorphism as a risk factor for Parkinson's disease

“…Additionally, patients with multiple system atrophy, a disease with a known α‐synuclein pathology, did not test positive for MOBP, and as such, MOBP seems to act independently of α‐synuclein. Regarding cortical LBs, the researchers also reported a small amount of MOBP 35 . Given that MOBP has been reported elevated in neurotoxic conditions in test subjects, 36 and that it does not seem to contribute to α‐synuclein aggregation, it is possible that its elevation reflects a compensatory mechanism that ultimately fails to protect the cells from degenerating.…”

MOBP rs616147 Polymorphism and Risk of Amyotrophic Lateral Sclerosis in a Greek Population: A Case-Control Study

“…The association of MOBP with other neurodegenerative diseases is well-established. To date, autoreactivity against MOBP has been detected among individuals with MS [13,15] and MOBP immunoreactivity has been detected in the core of Lewy Bodies (LBs) among patients with Parkinson' s disease and dementia with LBs [37,38]. MOBP SNPs have been associated with Apolipoprotein-E e4 positive AD [14], FTD (and the severity of white matter degeneration [16,39]), PSP [17,[40][41][42][43][44], Corticobasal Degeneration [43,44], while decreased expression of MOBP was revealed in familial Globular Glial Tauopathy [45] and differential DNA methylation of MOBP was shown in Multiple System Atrophy [46].…”