Multiple system atrophy: a primary oligodendrogliopathy.
To this day, the cause of multiple system atrophy (MSA) remains stubbornly enigmatic. A growing body of observations regarding the clinical, morphological, and biochemical phenotypes of MSA has been published, but the interested student is still left without a clue as to its underlying cause. MSA has long been considered a rare cousin of Parkinson's disease and cerebellar degeneration; it is rich in acronyms but poor in genetic and environmental leads. Because of the worldwide research efforts conducted over the last two decades and the discovery of the alpha-synuclein-encoding SNCA gene as a cause of rare familial Parkinson's disease, the MSA field has seen advances on three fronts: the identification of its principal cellular target, that is, oligodendrocytes; the characterization of alpha-synuclein-rich glial cytoplasmic inclusions as a suitable marker at autopsy; and improved diagnostic accuracy in living patients resulting from detailed clinicopathological studies. The working model of MSA as a primary glial disorder was recently strengthened by the finding of dysregulation in the metabolism of myelin basic protein and p25alpha, a central nervous system-specific phosphoprotein (also called tubulin polymerization promoting protein, TPPP). Intriguingly, in early cases of MSA, the oligodendrocytic changes in myelin basic protein and p25alpha processing were recorded even before formation of glial cytoplasmic inclusions became detectable. Here, we review the evolving concept that MSA may not just be related to Parkinson's disease but also share traits with the family of demyelinating disorders. Although these syndromes vary in their respective cause of oligodendrogliopathy, they have in common myelin disruption that is often followed by axonal dysfunction.
Wenning
Gregor K
GK
Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. gregor.wenning@i-med.ac.at
Stefanova
Nadia
N
Jellinger
Kurt A
KA
Poewe
Werner
W
Schlossmacher
Michael G
MG
D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D019578:Multiple System Atrophy / Q000473:pathology* / Q000503:physiopathology*; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology*; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; C118136:TPPP protein, human; D051844:alpha-Synuclein