Article Archive

Review: 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.

Review: 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.

Review: 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.

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

Published: 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.

Published: 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.

Published: 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.

Published: 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.

Published: 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.

Published: Selective autophagy is essential for maintaining cellular homeostasis. Using in vitro reconstitution, the authors explored the details of mitophagy initiation from autophagy receptor engagement through LC3 lipidation. They found that the core machinery engaged during mitophagy depends on different autophagy receptors, but LC3 lipidation is a universal feature. View original preprint.

Published: TBK1 mutations are linked to neurodegenerative disorders. The authors explored how TBK1 functions in PINK1/Parkin-dependent mitophagy and how mutations lead to disease. TBK1 recruitment and kinase activity contributed to the clearance of damaged mitochondria (mitophagy). Further, they showed that TBK1 presence alone could disrupt the mitochondrial network. View original preprint.

Published: Using embryonic stem-cell derived neurons to model age-related neurodegenerative diseases is inherently difficult. The authors thereby developed a chemical cocktail to induce cellular senescence (without causing DNA damage), thereby inducing embryonic cells to exhibit features characteristic of aged cells. The cocktail can help enhance disease-related phenotypes in iPSCs.

Review: This review focuses on the endolysosomal pathway roles of GBA and LRRK2, highlighting the role and activity of Rab GTPases as LRRK2 substrates.

Published: Genome-wide association studies (GWAS) reveal thousands of genetic loci. To understand the causality of the genetic variants, many researchers employ expression of quantitative trait locus (eQTL) analysis. The authors created a simplified, user-friendly R package called powerEQTL to aid in performing the power calculations needed for eQTL analysis. View original preprint.

Published: This methodology report assesses a large cohort of GBA mutation carriers with the goal of developing procedures to diagnose PD earlier. View original preprint.

Review: This review dissects the microbial contributions to PD with a particular focus on recent advances and rodent models that can be used for microorganism hypothesis testing.

Review: This review focuses on new insights into the stucture of LRRK2's cytosolic and microtubule-bound forms and challenges going forward.