Neuropathology of Multiple System Atrophy, a Glioneuronal Degenerative Disease

Abstract

Multiple system atrophy (MSA) is a fatal disease characterized pathologically by the widespread occurrence of aggregated α-synuclein in the oligodendrocytes referred to as glial cytoplasmic inclusions (GCIs). α-Synuclein aggregates are also found in the oligodendroglial nuclei and neuronal cytoplasm and nuclei. It is uncertain whether the primary source of α-synuclein in GCIs is originated from neurons or oligodendrocytes. Accumulating evidence suggests that there are two degenerative processes in this disease. One possibility is that numerous GCIs are associated with the impairment of oligo-myelin-axon-neuron complex, and the other is that neuronal inclusion pathology is also a primary event from the early stage. Both oligodendrocytes and neurons may be primarily affected in MSA, and the damage of one cell type contributes to the degeneration of the other. Vesicle-mediated transport plays a key role in the nuclear translocation of α-synuclein as well as in the formation of glial and neuronal α-synuclein inclusions. Recent studies have shown that impairment of autophagy can occur along with or as a result of α-synuclein accumulation in the brain of MSA and Lewy body disease. Activated autophagy may be implicated in the therapeutic approach for α-synucleinopathies.

Keywords: Autophagy; Glial cytoplasmic inclusion; Multi-system degeneration; Neuronal cytoplasmic inclusion; Vesicle-mediated transport; α-Synuclein.