Is Tau the Initial Pathology in Dopaminergic Nigrostriatal Degeneration? Studies in Parkinsonism and Parkinson’s Disease
By Blythe Lloyd onPreprint: 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.
Damaged mitochondria recruit the effector NEMO to activate NF-κB signaling
By Blythe Lloyd onPublished: 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.
Structural basis for ATG9A recruitment to the ULK1 complex in mitophagy initiation
By Blythe Lloyd onPublished: 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.
Unconventional Initiation of PINK1/Parkin Mitophagy by Optineurin
By Blythe Lloyd onPreprint: 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.
Integrated multi-cohort analysis of the Parkinson’s disease gut metagenome
By Blythe Lloyd onPreprint: 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 movement-related subthalamic nucleus activity in Parkinsonian mice
By Blythe Lloyd onPublication: 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 Directions
By taliag onReview: 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 disease
By taliag onPublished: 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.
In situ architecture of the lipid transport protein VPS13C at ER-lysosomes membrane contacts
By Blythe Lloyd onPublication: 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 nigral neuromelanin of Parkinson’s disease
By Blythe Lloyd onPublished: 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, authors investigated the relative composition and specific roles of pheomelanin and eumelanin moieties of NM in PD. View original preprint.
The IPDGC/GP2 Hackathon – an open science event for training in data science, genomics, and collaboration using Parkinson’s disease data
By taliag onOp-Ed: The authors outline the projects and results arising from the international ‘hackathon’, which was a 3-day collaborative event between the Global Parkinson’s Genetics Program (GP2) and the International Parkinson’s Disease Genomics Consortium (IPDGC).
Dystonia-Parkinsonism Gene Variants in Individuals with Parkinsonism and Brain Scans without Evidence for Dopaminergic Deficit (SWEDD)
By taliag onPreprint: The authors aimed to investigate the genetic etiology of dystonia-parkinsonism through examining individuals with DAT SPECT scans without evidence of dopamine defects (SWEDD). They found pathogenic variants in parkinsonian-dystonia genes occurred in more than 10% of SWEDD individuals.
Diversity in Parkinson’s disease genetics research: current landscape and future directions
By taliag onThis 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. This is a preprint.
Multi-Modality Machine Learning Predicting Parkinson’s Disease
By taliag onPublished: The authors performed automated machine learning on multi-modal data from PPMI and validated in the PDBP dataset. Further, they built networks to identify gene communities specific to PD. The model they built can improve multi-omic predictions of PD and improves disease risk prediction. View original preprint.
Large-scale biophysically detailed model of somatosensory thalamocortical circuits in NetPyNE
By taliag onPublished: The authors built a model of the primary sensory cortex (S1) in NetPyNE, using the data in the Neocortical Microcircuit Collaboration Portal. NetPyNE will make the S1 model more accessible and simpler to scale. View original preprint.
Multiscale model of primary motor cortex circuits predicts in vivo cell type-specific, behavioral state-dependent dynamics
By taliag onPublished: The authors developed a biophysically detailed multiscale model of mouse primary motor cortex (M1) with over 10,000 neurons and 30 million synapses. The model accurately predicted in vivo layer- and cell type-specific responses (firing rates and LFP) associated with behavioral states and experimental manipulations (noradrenaline receptor blocking and thalamus inactivation).
Unaltered T cell responses to common antigens in individuals with Parkinson’s disease
By taliag onPublished: T cells have been shown to be overactive in individuals with PD. The authors tested a wide variety of commonly encountered immune targets on PD and non-PD control derived T cells and observed no differences between their immune responses. View original preprint.
Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures
By taliag onPublished: Recent findings identified PD-associated autoimmune features. Using RNA sequencing, the authors found a broad gene expression profile in memory T cells and a specific PD-associated gene signature. Slpha-synuclein responding T cell gene expression profiles were associated with dysregulation in multiple cellular pathways related to PD genes. View original preprint.
Genetic and pharmacological reduction of CDK14 mitigates α-synuclein pathology in human neurons and in rodent models of Parkinson’s disease
By taliag onPreprint: Decreasing alpha-synuclein levels is a potential therapeutic approach for synucleinopathies. The authors identified CDK14 regulates alpha-synuclein and show reduction of CDK14 in two different PD mouse models reduces alpha-synuclein and PD-like characteristics. They also demonstrate that inhibiting CDK14 with a drug lowers alpha-synuclein burdens in rodent and human neurons.
Towards a phenome-wide view of Parkinson’s disease
By taliag onPreprint: The authors examine that relationship between PD and the environment by holistically characterizing environmental, health, and pharmacological traits associated with PD patients. They found numerous traits that were positively and negatively associated with PD.