{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent genomic investigations have revealed that myelin‐associated oligodendrocyte basic protein (MOBP) plays a role as a susceptibility gene in several neurodegenerative disorders. Genome‐wide association studies have identified MOBP as a novel risk locus in amyotrophic lateral sclerosis (ALS) and have linked genetic variability at this locus with corticobasal degeneration, progressive supranuclear palsy, and even Alzheimer’s disease in specific genetic contexts (e.g., APOE ε4 carriers). While one study demonstrated that MOBP is among the new risk loci for ALS, another found significant associations in tauopathies such as corticobasal degeneration and progressive supranuclear palsy, further supporting the involvement of MOBP in neurodegenerative processes. Notably, investigations of the rs616147 polymorphism within MOBP have produced contrasting findings, with some cohorts reporting an association with ALS risk and others, particularly in populations of Greek ancestry, not confirming such an effect."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its genetic associations, alterations in MOBP expression and epigenetic regulation have been documented in various pathological contexts. In human cocaine abusers, for instance, microarray and RT-PCR analyses have revealed an aberrant regulation of myelin-associated genes, including a decrease in MOBP transcript levels in key brain regions involved in reward processing. Conversely, increased MOBP mRNA expression was observed in the dorsolateral prefrontal white matter of patients with a history of substance abuse, suggesting that MOBP expression may be dynamically modulated by environmental or toxic insults. In parallel, studies on multiple system atrophy have identified MOBP as one of the most differentially methylated loci, and network-based DNA methylation analyses imply that such epigenetic changes could have downstream consequences on gene regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the protein level, MOBP is fundamentally known for its role in maintaining the structural integrity of the myelin sheath in the central nervous system. Immunohistochemical studies have demonstrated that in healthy brains, MOBP localizes predominantly to myelin as well as neuronal cytoplasm across both central and peripheral nervous systems. Of particular interest, in Parkinson’s disease and dementia with Lewy bodies, MOBP immunoreactivity is robustly present in the cores of Lewy body inclusions, which may indicate a compensatory or cytoprotective response to pathological protein aggregation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ""}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wouter van Rheenen, Aleksey Shatunov, Annelot M Dekker, et al. 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