The emerging role of LRRK2 in tauopathies
By Blythe Lloyd onReview: Authors review the emerging evidence and discuss the potential impact of LRRK2 dysfunction on tau aggregation, lysosomal function, and endocytosis and exocytosis.
Pathological structural conversion of α-synuclein at the mitochondria induces neuronal toxicity
By Blythe Lloyd onPublished: 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 Electrophysiology (Mouse)
By Blythe Lloyd onThis protocol describes the in vivo electrophysiology method for recording neuronal activity in mice.
Immunohistochemistry
By Blythe Lloyd onThis protocol describes immunohistochemical staining of fixed brain sections.
Imaris Coloc Protocol
By Blythe Lloyd onImaris intensity-based protocol for Colocalization analysis.
GUV assay
By Blythe Lloyd onThis protocol describes the preparation of GUVs for the reconstitution of LC3 lipidation reaction through the steps of PI3P production by PI3KC3-C1, WIPI2 recruitement and LC3 lipidation with PE. Screen reader support enabled.
In vivo reduction of age-dependent neuromelanin accumulation mitigates features of Parkinson’s disease
By Blythe Lloyd onPublished: 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 stability
By Blythe Lloyd onPublication: 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.
Nicotine-mediated rescue of α-synuclein toxicity requires synaptic vesicle glycoprotein 2
By Blythe Lloyd onPublished: 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 lines
By Blythe Lloyd onPublished: 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.
Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms
By Blythe Lloyd onPublished: 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 fluid
By Blythe Lloyd onPreprint: 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 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.