α-Synuclein aggregation has been linked to Gaucher's disease (GD) and Krabbe's disease (KD), lysosomal conditions affecting glycosphingolipid metabolism.
Here, we used a multi-pronged approach including genetic, biophysical and biochemical techniques to determine the pathogenic contribution, reversibility, and molecular mechanism of aggregation of α-synuclein in KD.
Similarities between the two diseases, including the pattern of α-synuclein aggregation in the brain of the twitcher mouse (the authentic murine model of Krabbe's disease), changes to lipid membrane dynamics, and possible dysfunction in synaptic function and macroautophagy, underscore a link between Krabbe's disease and late-onset synucleinopathies.