Collaborative Research Network Archive

For unclear reasons, PD patients with certain GBA1 mutations (GBA-PD) have a more aggressive clinical progression. The authors tested the two hypotheses for why this occurs; that GBA1 mutations promote αsyn spread or drive the generation of highly pathogenic αsyn polymorphs (i.e., strains).

The authors show that Parvalbumin interneurons that are inhibitory regulators of movement also lose primary cilia.

Parkinson’s disease-associated, activating mutations in LRRK2 block primary cilia formation, decreasing the production of neuroprotective factors that support dopaminergic neuron viability. The authors show that pathogenic LRRK2-driven cilia loss is reversible in post-mitotic neurons and astrocytes.

The used array fiber photometry in mice to investigate how ACh release across the striatum evolves during learning and extinction of Pavlovian associations.

The authors tested different detergents for their ability to solubilize human α-synuclein carrying the pathological mutation A53T from the brains of aged flies.

Evidence is mounting that injury and inflammation in the gut and locus coeruleus (LC), respectively, underlie Parkinson's disease symptoms, and the injury of these systems is central to the progression of PD. In this study, the authors generate a novel two-hit mouse model that captures both features.

To identify shared and distinct features of the PD and IBD microbiome, the authors performed a joint analysis of 54 PD, 26 IBD, and 16 healthy control gut metagenomes recruited from clinics at the University of Florida and directly compared the gut microbiomes from PD and IBD persons.

Many motor behaviors require learning through repeated practice. Among the brain’s motor regions, the cortico-basal ganglia circuit is particularly crucial for acquiring and executing motor skills, and neuronal activity in these regions is directly linked to movement parameters. Here, the authors detail the cortico-basal ganglia plasticity in motor learning.

This article summarizes the most up-to-date knowledge in pharmacomicrobiomics in PD, and discusses how the manipulation of gut microbiota represents a potential new therapeutic avenue for PD.

The authors explored the cellular and synaptic mechanisms of levodopa-induced dyskinesia (LID), a complication of Parkinson’s disease therapy characterized by involuntary movements. Findings suggest how the intrinsic and synaptic properties of heterogeneous dMSN subpopulations integrate to support action selection.

Publication: These results suggest that the limited efficiency of autophagy in clearing polyQ aggregates is due to the inability of autophagosomes to interact productively with the non-deformable, fibrillar disease aggregates. View original preprint.