ATP13A2-mediated endo-lysosomal polyamine export counters mitochondrial oxidative stress
By taliag onPublished: 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 Regulates Cellular α-Synuclein Multimerization, Membrane Association, and Externalization
By taliag onPublished: 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.
Subcellular proteomics of dopamine neurons in the mouse brain
By taliag onPublished: 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. View original preprint.
Subcellular and regional localization of mRNA translation in midbrain dopamine neurons
By taliag onPublished: Midbrain dopaminergic neurons have broad dendritic and axonal arborizations, but local protein synthesis is not understood here. Using, highly sensitive ribosome-bound RNA sequencing and imaging to characterize the translatome, the authors uncovered local mRNA translation of dopamine synthesis, release, and reuptake machinery in dendrites, but not axons. View original preprint.
Constitutive nuclear accumulation of endogenous alpha-synuclein in mice causes motor impairment and cortical dysfunction, independent of protein aggregation
By taliag onPublished: Nuclear alpha-synuclein may play a role in the pathogenesis of PD. To study this, the authors engineered SncaNLS mice that exhibit endogenous alpha-synuclein in the nucleus. After behavioral, histological, and biochemical analysis of the mice, the authors found that chronic nuclear alpha-synuclein can create toxic cellular phenotypes, independent of aggregation.