Assaying starvation-induced autophagy in HeLa cells
By Blythe Lloyd onA method for assaying starvation-induced autophagy in HeLa cells that have been transfected with Halo-tagged constructs. This protocol was specifically used to investigate the impact of various mutations in the protein WIPI2 on starvation-induced autophagy in cells.
Analysis of glycosphingolipids from human plasma
By Blythe Lloyd onThe original qualitative method was published in 2004 and measured the oligosaccharides selectively released from glycosphingolipids using a ceramide glycanase enzyme derived from the medicinal leech. This is an updated protocol with the focus on achieving sensitive and reproducible quantitation of glycosphingolipids from human plasma samples
Activation Induced Marker (AIM) Staining Protocol
By Blythe Lloyd onThis protocol details about activation induced marker staining.
Jensen_etal_2022_membrane_tube_images
By Blythe Lloyd onMembrane tube assay data for Jensen et al, 2022
Damaged mitochondria recruit the effector NEMO to activate NF-κB signaling
By Blythe Lloyd onAll datasets associated with the "Damaged mitochondria recruit the effector NEMO to activate NF-κB signaling" article. DOI:10.1101/2022.06.21.496850
RHReynolds/neurodegen-psych-local-corr: Code to determine local and global genetic correlations between several neurodegenerative and neuropsychiatric disorders with LAVA and LDSC, respectively.
By Blythe Lloyd onCode for the paper: Local genetic correlations exist among neurodegenerative and neuropsychiatric diseases: https://doi.org/10.1101/2022.05.30.22275781
huw-morris-lab/PDD_GWSS
By Blythe Lloyd onCode used in the analysis from the manuscript Real et al., Association between the LRP1B and APOE loci and the development of Parkinson’s disease dementia (2022): https://doi.org/10.1101/2022.05.23.22275465
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.
The activities of LRRK2 and GCase are positively correlated in clinical biospecimens and experimental models of Parkinson’s disease
By taliag onRecent 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. This is a preprint.
Highly efficient generation of isogenic pluripotent stem cell models using prime editing
By taliag onPublished: Genetically engineered human pluripotent stem cells (hPSCs) containing specific mutations are invaluable for assessing the impact of gene mutations on disease pathology. The authors generated mutated hPSCs through utilization of a novel prime editing-based genome editing platform. Additionally, they show that our system can correct a known Parkinson’s disease-associated mutation. View original preprint here.
Structural basis for Parkinson’s Disease-linked LRRK2’s binding to microtubules
By taliag onPreprint: LRRK2 mutations are a common cause of familial PD. In some circumstances, LRRK2 co-localizes with microtubules. The authors report a cryo-electron microscopy structure of the catalytic half of LRRK2, containing its kinase (closed conformation) and GTPase domains, bound to microtubules. Further, they identified amino acids that mediate microtubule binding.
Membrane curvature sensing and stabilization by the autophagic LC3 lipidation machinery
By taliag onPreprint: During autophagy initiation, the curved phagophore is stabilized. Using in vitro reconstitution, the authors show that WIPI2 and ATG16L1 bind these curved phagophores, WIPI2 binding directs membrane recruitment, and the ATG12-5-16L1 complex is responsible for membrane curvature.
In situ structural analysis reveals membrane shape transitions during autophagosome formation
By taliag onPreprint: A hallmark of PD is the failure of quality control mechanisms in the cell, such as autophagy. The authors combined cell biology with correlative cryo-electron tomography in yeast cells to show a high resolution stepwise structural progression of autophagosome biogenesis. Further, they revealed the organelle interactome for growing autophagosomes.
The AAA+ chaperone VCP disaggregates Tau fibrils and generates aggregate seeds in a cellular system
By taliag onPublished: Protein aggregates, like tau, are associated with neurodegenerative diseases. Of interest is the cellular mechanism by which protein aggregates are removed. The authors show that the AAA+ chaperone, VCP, is recruited to ubiquitylated Tau, resulting in disaggregation. This finding identifies a role for VCP, Hsp70, and the ubiquitin-proteasome system. View original preprint.