Reciprocal effects of alpha-synuclein aggregation and lysosomal homeostasis in synucleinopathy models

ConclusionsOur findings demonstrate a strong interplay between αSyn aggregation pathways and function of lysosomal cathepsins. It appears that αSyn directly interferes with the enzymatic function of cathepsins, which might lead to a vicious cycle of impaired αSyn degradation.Graphical abstractLysosomal trafficking of cathepsin D (CTSD), CTSL and CTSB is disrupted when alpha-synuclein ( αSyn) is aggregated. This results in a decreased proteolytic activity of cathepsins, which directly mediate αSyn clearance. Boosting the transport of the cathepsins to the lysosome increases their activity and thus contributes to efficient αSyn degradation.
Source: Translational Neurodegeneration - Category: Neurology Source Type: research