Multiple system atrophy (MSA) is a rare adult-onset, sporadic, progressive neurodegenrative disorder that manifests with autonomic, parkinsonian, cerebellar, and pyramidal features. MSA belongs to the neurodegenerative group of α-synucleinopathies, which is characterized by the accumulation of misfolded α-synuclein (αSyn) in oligodendroglia and neurons, affecting multiple parts of the central, autonomic and peripheral system.
The genetic component of MSA has been proposed while the pathogenesis and etiology remain unknown. Accumulation of aberrant αSyn in oligodendrocytes, preceded by relocation of p25α protein from myelin into oligodendroglia, leads to the the formation of insoluble glial cytoplasmic inclusions (GCIs). These changes are associated with several dysfunctions such as
The functioning of the oligodendroglial-myelin-axon-neuron complex gets affected, resulting in the system-specific pattern of neurodegeneration characterizing MSA as a synucleinopathy with oligodendroglio-neuronopathy. Propagation of modified toxic αSyn species from neurons to oligodendroglia by "prion-like" transfer and its spreading to associate neuronal pathways result in multi-system involvement.Prominent targets for disease therapy include
Combination therapies, eg, immunotherapy against αSyn + antiinflammatory agents or multi-target drugs may be the next step for the treatment of synucleinopathies. A new European project (SYMPATH) is currently assessing a vaccine targetting αSyn (AFFITOPE) in PD and MSA in humans.