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.
In vivo reduction of age-dependent neuromelanin accumulation mitigates features of Parkinson’s diseaseon
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.
The Parkinson’s disease protein alpha-synuclein is a modulator of Processing-bodies and mRNA stabilityon
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.
The GBA variant E326K is associated with alpha-synuclein aggregation and lipid droplet accumulation in human cell lineson
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.
Structural and functional landscape of α-synuclein fibrilconformations amplified from cerebrospinal fluidon
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.
Is Tau the Initial Pathology in Dopaminergic Nigrostriatal Degeneration? Studies in Parkinsonism and Parkinson’s Diseaseon
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.
Preprint: 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.
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.
Therapeutic Deep Brain Stimulation Disrupts Subthalamic Nucleus Activity Dynamics in Parkinsonian Miceon
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.
Underrepresented Populations in Parkinson’s Genetics Research: Current Landscape and Future Directionson
Review: This review provides an overview of research involving PD genetics in under-represented populations, setting a baseline to measure future impact. The authors found a significant lack of population diversity in PD research, highlighting the need for more representation. View original preprint.
LRRK2 kinase activity regulates GCase level and enzymatic activity differently depending on cell type in Parkinson’s diseaseon
Published: Recent work suggests that LRRK2 kinase activity can modulate glucocerebrosidase (GCase) function. The authors investigated the relationship between LRRK2 and GBA1 by assessing GCase activity and found a positive correlation between the activities of LRRK2 and GCase in different cellular and ex vivo models. View original preprint.
Publication: Loss-of-function mutations in VPS13C are responsible for rare cases of familial early onset Parkinson’s disease. Using cryo-ET, the authors provide in-situ evidence for a bridge-model of VPS13 in lipid transport. View the original preprint.
DOPA pheomelanin is increased in neuromelanin of Parkinson’s disease substantia nigra and it exacerbates alpha-synuclein neurotoxicityon
Preprint: Neuromelanin in the substantia nigra may be a key factor contributing to dopaminergic neuron vulnerability in Parkinson’s disease. Neuromelanin consists of pheomelanin and eumelanin moieties. Here, the authors investigated the relative composition and specific roles of pheomelanin and eumelanin moieties of NM in PD.