Figure 3. Key mechanisms underlying neurodegeneration in MSA.

(a) The precise mechanisms underlying neurodegeneration in MSA remain to be resolved, however, emerging results from studies on MSA and other α-synucleinopathies have highlighted a number of key pathways, including oxidative stress, perhaps as a result of mitochondrial dysfunction, environmental exposure to toxins, or a combination of both. (b) The pathological accumulation of oligodendroglial α-syn, possibly a result of cell-to-cell transfer of the protein, may potentiate neurodegeneration by a lack of trophic support for the neuron or by altered myelination. (c) The eventual macroscopic effect of these mechanisms is widespread atrophy in MSA brains. Image of the control brain is Nissel stained and adapted with permission from http://www.brains.rad.msu.edu, (supported by the US National Science Foundation). The image of the MSA brain is stained with Holzer stain, and reproduced, with permission from ¹¹⁶.