Mitochondria purification
By Emma Sherrell onThis protocol describes how to purify mitochondria from cell culture.
Co-immunoprecipitation
By Emma Sherrell onThis protocol describes a common procedure to perform co-immunoprecipitation.
Medium fractionation and EV preparation
By Emma Sherrell onThis protocol describes the characterization of the extracellular alpha-synuclein and DNAJC5.
CRISPR/Cas9 genome editing
By Emma Sherrell onThis protocol describes the generation of DNAJC5 KO using CRISPR/Cas9 edition.
In vitro depalmitoylation assay
By Emma Sherrell onThis protocol describes the in vitro depalmitoylation assay of DNAJC5.
Membrane and cytosol fractionation
By Emma Sherrell onThis protocol describes membrane and cytosol fractionation of cells expressing different DNAJC5 isoforms.
LRRK2 kinase inhibition reverses G2019S mutation-dependent effects on tau pathology spread
By Emma Sherrell onPublished: Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson’s disease (PD). This work supports a protective role of LRRK2 kinase inhibition in G2019S carriers and provides a rational workflow for systematic evaluation of brain-wide phenotypes in therapeutic development. View original preprint.
A topographical atlas of αSyn dosage and cell-type expression in the mouse brain and periphery
By Emma Sherrell onPublished: Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide and presents pathologically with Lewy pathology and dopaminergic neuron loss. This atlas provides much-needed insight into the cellular topography of αSyn, and provides a quantitative map to test assumptions about the role of αSyn in network vulnerability in PD and other αSynucleinopathies. View original preprint.
iATPSnFR2: a high dynamic range fluorescent sensor for monitoring intracellular ATP
By Emma Sherrell onPreprint: Subcellular targeting of the sensor to nerve terminals reveals previously uncharacterized single synapse metabolic signatures, while targeting to the mitochondrial matrix allowed direct quantitative probing of oxidative phosphorylation dynamics.
Phosphoglycerate kinase is a central leverage point in Parkinson’s Disease driven neuronal metabolic deficits
By Emma Sherrell onPreprint: The data indicates that nerve terminal bioenergetic deficits may underly a spectrum of PD susceptibilities and the identification of PGK1 as the limiting enzyme in axonal glycolysis provides a mechanistic underpinning for therapeutic protection.
Systems-level analyses dissociate genetic regulators of reactive oxygen species and energy production
By Emma Sherrell onPreprint: The authors'results identify specific metabolic regulators of cellular ATP and ROS balance that may help dissect the roles of these processes in disease and identify therapeutic strategies to independently target energy failure and oxidative stress.
M4-mediated cholinergic transmission is reduced in Parkinsonian mice and its restoration alleviates motor deficits and levodopa-induced dyskinesia
By Emma Sherrell onPreprint: Despite M4-receptors being thought to mediate anti-kinetic effects, restoring M4-receptor function partially rescued Parkinsonian balance and coordination deficits and limited the development of levodopa-induced dyskinetic behaviors, indicating that decreased M4-function contributed to circuit and motor dysfunctions in response to DA loss.
Adaptor protein-3 produces synaptic vesicles that release phasic dopamine
By Emma Sherrell onThe burst firing of midbrain dopamine neurons releases a phasic dopamine signal that mediates reinforcement learning. AP-3 and VPS41 promote the axonal polarity of dopamine release but enable learning by producing a distinct population of SVs tuned specifically to high firing frequency that confers the phasic release of dopamine.
Next-generation sequencing of AAV.CAP-Mac enrichment from Chuapoco et al. (2023)
By Emma Sherrell onDataset of next-generation sequencing of enrichment of AAV.CAP-Mac in various tissues from the publication: Chuapoco, M.R., Flytzanis, N.C., Goeden, N. et al. Adeno-associated viral vectors for functional intravenous gene transfer throughout the non-human primate brain. Nat. Nanotechnol. (2023). https://doi.org/10.1038/s41565-023-01419-x
LBD-case-case-GWAS
By Emma Sherrell onCode used in the analysis from the manuscript Wu et al., Investigation of the genetic aetiology of Lewy body diseases with and without dementia (2023).
Investigation of the genetic aetiology of Lewy body diseases with and without dementia
By Emma Sherrell onPublished: The authors found that risk alleles rs429358 tagging APOEe4 and rs7668531 near the MMRN1 and SNCA-AS1 genes, increase the odds of developing dementia and that an intronic variant rs17442721 tagging LRRK2 G2019S, on chromosome 12 is protective against dementia. These results should be validated in autopsy confirmed cases in future studies. View original preprint.
UniProtExtractR: an app and R package for easily extracting protein-specific UniProtKB information and fine-tuning organelle resolution
By Emma Sherrell onThe app features interactive frequency tables that globally summarize both the original UniProtKB input query as well as the extracted/changed entry values. Moreover, UniProtExtractR includes a tractable mapping algorithm to define custom organelle-level resolution.
UniProtExtractR
By Emma Sherrell onThe app features interactive frequency tables that globally summarize both the original UniProtKB input query as well as the extracted/changed entry values.
Proteome census upon nutrient stress reveals Golgiphagy membrane receptors
By Emma Sherrell onDuring nutrient stress, macroautophagy is employed to degrade cellular macromolecules, thereby providing biosynthetic building blocks while simultaneously remodeling the proteome. The authors' results, available via an interactive web tool, reveal that autophagic turnover prioritizes membrane-bound organelles (principally Golgi and ER) for proteome remodeling during nutrient stress.
Strep-pull down assay
By Emma Sherrell onStrep pull down assay for FIP200(NTD)-TSF WT or mutants were co-transfected with GST-ATG13(363-517) and/or ULK1(MIT)-MBP.