Article Archive

Publication: The authors previously showed that MC1R signaling can facilitate nigrostriatal dopaminergic neuron survival. The present study investigates the neuroprotective potential of MC1R against neurotoxicity induced by alpha-synuclein, a key player in PD genetics and pathogenesis. View original preprint.

Publication: The role of tau in the development of αS pathology and subsequent neuronal dysfunction has been controversial. Herein, the authors examine the role of tau in the onset and progression of αS pathology using a transgenic mouse model of α-synucleinopathy lacking mouse tau expression. View original preprint.

Publication: In this study, the lipid membrane composition of fibroblasts isolated from control subjects, patients with idiopathic Parkinson's disease and Parkinson's disease patients carrying the L444P GBA mutation (PD-GBA) was assayed using shotgun lipidomics. Findings suggest that L44P GBA mutations have a distinctly altered membrane lipid profile. View original preprint.  

Publication: Learning and consolidating new motor skills require plasticity in the motor cortex and striatum, two key motor regions of the brain. However, how neurons undergo synaptic changes and become recruited during motor learning to form a memory remains unknown. Here the authors identify M1 engram neurons important for memory.

Publication: The gut microbiome is altered in PD and may impact motor and GI symptoms as indicated by animal studies, although mechanisms of gut-brain interactions remain incompletely defined. Here, the authors investigated whether a fiber-rich diet influences microglial function in α-synuclein overexpressing (ASO) mice, a preclinical model with PD-like symptoms and pathology. View original preprint.  

Publication: LRRK2 mutations are closely associated with PD. Convergent evidence suggests that LRRK2 regulates striatal function. Here, by using knock-in mouse lines expressing the two most common LRRK2 pathogenic mutations – G2019S and R1441C – the authors investigated how LRRK2 mutations altered striatal physiology. View original preprint.  

Preprint: Gain-of-function mutations in the LRRK2 gene cause Parkinson's disease (PD), increasing phosphorylation of RAB GTPases through hyperactive kinase activity. The authors found that LRRK2-hyperphosphorylated RABs disrupt the axonal transport of autophagosomes by perturbing the coordinated regulation of cytoplasmic dynein and kinesin motors.  

Published: In this article, the authors explored whether there are genetic variants that explain variability in the motor progression found in Parkinson’s in clinical cohorts. They performed a large study genome scan looking at the influence of genetic variation on motor progression and the worsening of motor capabilities among thousands of Parkinson's patients. View original preprint.  

Preprint: Genetic analyses are often complicated by genomic sequences with high sequence similarity. Here, the authors examined the role of pseudogenes on transcriptomic analyses using GB1 and GBAP1 as examples.

Published: The authors developed Sniffles2, a faster and more accurate method to analyze long-ready structural variation calling. This method also solves the problem of family to population-level SV calling to produce fully genotyped VCF files. View original preprint.

Published: The authors explored the role of resident macrophages in alpha-synuclein-mediated neuroinflammation. They found that border-associated macrophages (BAMs) play a key role in alpha-synuclein induced neuroinflammation where BAMs play a role in immune cell recruitment, infiltration, and antigen presentation. View original preprint.  

Preprint: Evidence suggests that disruption of autophagy may contribute to PD pathogenesis. Yet, the role it plays is unresolved. The authors used unbiased proteomics to compare basal autophagy to autophagy in two PD-relevant mouse models (PINK1 KO and LRRK2 G2019S). They found different compensatory mechanisms to maintain cellular homeostasis when autophagy is disrupted.

Preprint: Mutations in the SNCA gene causes PD and aggregates of alpha-synuclein are well known to be present in PD pathology. However, understanding the cellular sequence of events that occurs from mutation to pathology is unresolved. The authors find the temporal sequence of pathophysiological events that occur during neuronal differentiation that likely cause synucleopathies.

Published: The authors explore how cellular energy production and demand are matched. By studying the pacemaking activity of dopaminergic neurons using a combination of electrophysiolocal, optical, and molecular method, they found that spike- activated calcium ion entry triggered calcium ion release from the ER, causing mitochondrial oxidative phosphorylation to occur through two calcium-dependent mechanisms.