Article Archive

Review: A discussion on learnings from phase 1 clinical trial for kinase inhibitors targeting LRRK2 that can provide the foundations for moving towards testing the efficacy of LRRK2 kinase inhibition in Parkinson’s disease.

Review: Authors provide an overview of the immunobiology of Parkinson’s disease, focusing on the role α-synuclein in the gut-brain axis hypothesis, the innate and adaptive immune responses involved in the disease, and current treatments.

Here, the authors review recent work utilizing metabolic tracing to study health and disease, and highlight its application to interrogate subcellular, intercellular, and in vivo metabolism. The authors further discuss the current challenges and opportunities to expand the utility of isotope tracing to new research areas.

Review: Here, authors summarize the contributions of membrane contact sites in dysregulation of inter-organellar communication, taking findings from Parkinson's and Alzheimer's as major examples.

Review: Authors highlight the important work being done that implicates central and peripheral inflammation in playing a role in PD. They also discuss how these two distant inflammations appear related and how that may be mediated by autoantigenic responses to α-synuclein.

Review: Authors review the history of studying gut-brain interactions and offer a forward-looking perspective on the future of microbiota-gut-brain research.

Review: Authors review the emerging evidence and discuss the potential impact of LRRK2 dysfunction on tau aggregation, lysosomal function, and endocytosis and exocytosis.

Published: Using a single molecule FRET sensor, the authors track the intracelleular conformational states of alpha-synucelin and where these occur in the cell. The study suggests that oligomerization happens at the mitochonodria triggering neuronal toxicity. View original preprint.

Published: Using a newly developed rodent model, the authors assessed whether the intracellular buildup of neuromelanin that occurs with age can be slowed down in vivo to prevent or attenuate Parkinson’s disease. When neuromelanin reaches a specific threshold, it can trigger PD pathology in this animal model. View original preprint.

Publication: The paper describes a new function for alpha synuclein - an ability to bind to structures known as a "P-body". P-body machinery in the cell regulates the expression of our genes through mRNAs. When alpha-synuclein abnormally accumulates, the physiologic structure and functions of the P-body are lost.

Published: Parkinson's disease likely reflects a complex interaction among genetic and environmental factors. Here, the role of nicotine, SV2 and the alpha-synuclein were examined. The study suggests that SV2 may be needed for the protection nicotine provides from Parkinson's-related neurotoxicity. View original preprint.

Published: The GBA variant E326K is associated with alpha-synuclein aggregation and lipid droplet accumulation in human cell lines, (x6) GBA het and hom mutant fibroblasts. View original preprint.

Published: This work looked at a recently generated gut metagenome dataset and characterized the altered PD microbiome at species, gene, and pathway levels. They found 30% of species and pathways either elevated or depleted in PD, depicting a far more complex and widespread dysbiosis than previously known. View original preprint.

Preprint: Using cryo-electron microscopy to look at alpha-synuclein structurs in the cerebral spinal fluid from those diagnosed with lewy body dementia, the authors identify novel structures highlighting the different ways that alpha-synucelin can fold and assemble.

Preprint: Here, the authors look at whether nigrostriatal dopaminergic neurodegeneration occurs independently of alpha-synuclein aggregation for those living with PD. Their findings suggest that it is independent and likely tau mediated.

Published: The connections between molecular mechanisms like mitophagy and tissue-wide features like neuro-inflammation remain unclear. Here, the authors characterize a novel link between these two hallmarks of neurodegeneration.

Published: Here, the authors examine the structural interaction between ATG0A and components of the ULK1 complex to better understand the process of the PINK1- and Parkin- dependent mitophagy pathway implicated in Parkinson's disease. View original preprint.

Preprint: Cargo sequestration is a fundamental step of selective autophagy in which cells generate a double membrane structure termed an autophagosome on the surface of cargoes. How OPTN initiates autophagosome formation during selective autophagy remains unknown despite its importance in neurodegeneration. The authors uncover an unconventional path of PINK1/Parkin mitophagy initiation by OPTN.

Preprint: Here, the fecal metagenomes of those living with PD compared to others in the household were profiled from 4 geographically-distinct sites across 3 continents. The question was whether there were any specific PD-associated signatures in gut microbiome that are either enriched or depleted in PD.

Publication: Subthalamic nucleus deep brain stimulation relieves many motor symptoms of Parkinson’s disease, but its underlying therapeutic mechanisms remain unclear. Here, authors used electrical artifact-free GCaMP fiber photometry to investigate activity in basal ganglia nuclei during STN DBS in parkinsonian mice to get at that question. View original preprint.