Collaborative Research Network Archive

This review focuses on understanding the PINK1/Parkin-mediated mitochondrial quality control pathway through the lens of abherrant immune activation as a driver of dopaminerigic neuron loss following the loss of PINK and Parkin.

This review summarizes parkinsonian phenotypes in rodent models targeting genes that have a role in endolysosomal pathways and future steps to better understand the contribution of endolysosomal dysfunction to PD.

This review summarizes key technological advances that have led to a better understanding of the contribution of the lysosome to neurodegeneration and highlights key questions to be addressed moving forward.

This review focuses on the role that the lysosome plays in maintaining iron homeostasis and how lysosomal iron dysregulation contributes to disease.

Loss-of-function of ATP13A2, an endo-lysosomal transporter that pumps polyamines into the cytosol, is associated with PD. ATP13A2 dysfunction causes polyamine accumulation within the lysosome and lysosomal rupture. The authors found a conserved cellular protective pathway involving ATP13A2-mediated lysosomal spermine export to provide protection against mitochondrial toxins.

ATP13A2 loss-of-function mutations cause lysosomal deficiency and are linked to Parkinson’s disease and alpha-synuclein pathology. The authors found that loss of ATP13A2 disrupts lysosomal membrane integrity and causes alpha-synuclein multimerization. Further, they showed that increased levels of ATP13A2 had a protective effect on alpha-synuclein aggregation.

Understanding the proteome of dopamine neuron is difficult due to the complex cytoarchitecture of the neurons. The authors were able to map the somatodendritic and axonal proteomes of midbrain dopaminergic neurons. Interestingly, the authors found striatal dopaminergic neurons house most proteins.