A leaky gut dysregulates gene networks in the brain associated with immune activation, oxidative stress, and myelination in a mouse model of colitis
By Emma Sherrell onPreprint: The team provides a comprehensive evaluation of multiple systems in a prevalent experimental model of intestinal permeability, which will inform future studies using this model and others, assist in the identification of druggable targets in the gut-brain axis, and contribute to our understanding of the concomitance of intestinal and neuropsychiatric dysfunction.
The R1441C-LRRK2 mutation induces myeloid immune cell exhaustion in an age- and sex-dependent manner
By Emma Sherrell onPreprint: LRRK2 has become an appealing target in PD, but findings suggest that more research is required to understand the cell-type-specific consequences and optimal timing of LRRK2-targeting therapeutics.
Calcium influx into astrocytes plays a pivotal role in inflammation-driven behaviors
By Emma Sherrell onGraphical abstract.
Gut mucosal cells transfer α-synuclein to the vagus nerve
By Emma Sherrell onPublished: These findings highlight a potential non-neuronal source of fibrillar α-synuclein protein that might arise in gut mucosal cells. View original preprint.
Comparative analysis of methods to reduce activation signature gene expression in PBMCs
By Julia Julia Leonard onPreprint: These findings highlight the importance of considering the advantages and drawbacks of different isolation methods to ensure accurate interpretation of PBMC transcriptomic profiles.
VPS13B is localized at the cis-trans Golgi complex interface and is a functional partner of FAM177A1
By Julia Julia Leonard onPreprint: These findings raise the possibility that bulk lipid transport by VPS13B may play a role in expanding Golgi membranes and that VPS13B may be assisted in this function by FAM177A1.
A STING-CASM-GABARAP pathway activates LRRK2 at lysosomes
By Julia Julia Leonard onPreprint: These results define a pathway that integrates multiple stimuli at lysosomes to control the kinase activity of LRRK2. Aberrant activation this pathway may be of relevance in both Parkinson’s and Crohn’s diseases.
Lysosomal TBK1 responds to amino acid availability to relieve Rab7-Dependent mTORC1 inhibition
By Julia Julia Leonard onPreprint: Data establishes the lysosome as a site of amino acid regulated TBK1 signaling that is crucial for efficient mTORC1 activation. This lysosomal pool of TBK1 has broader implications for lysosome homeostasis, and its dysregulation could contribute to the pathogenesis of ALS-FTD.
A fluid-walled microfluidic platform for human neuron microcircuits and directed axotomy
By Julia Julia Leonard onPreprint: Cortical axons in conduits are severed by a media jet; then, brain-derived neurotrophic factor and striatal neurons in distal chambers promote axon regeneration. As additional conduits and chambers are easily added, this opens up the possibility of mimicking complex neuronal networks and screening drugs for their effects on connectivity.
Three-step docking by WIPI2, ATG16L1 and ATG3 delivers LC3 to the phagophore: Molecular dynamics simulation dat
By Emma Sherrell onAtomistic molecular dynamics simulation data set accompanying manuscript "Three-step docking by WIPI2, ATG16L1 and ATG3 delivers LC3 to the phagophore."
Peripheral MC1R activation modulates immune responses and is neuroprotective in a mouse model of Parkinson’s disease
By Julia Julia Leonard onPreprint: The present study investigates the impact of NDP-MSH, a synthetic melanocortin receptor (MCR) agonist that does not cross BBB, on the immune system and the nigrostriatal dopaminergic system in mouse model of PD.
Mechanism of human PINK1 activation at the TOM complex in a reconstituted system
By Julia Julia Leonard onPreprint: The authors demonstrate an essential role of the pore-containing subunit TOM40 and its structurally associated subunits TOM7 and TOM22 for PINK1 activation. These molecular findings will aid in the development of small molecule activators of PINK1 as a therapeutic strategy for PD.
Unique functional responses differentially map onto genetic subtypes of dopamine neurons
By savannah onPublished: Genetic strategies to isolate dopaminergic subtypes lead to the establishment of a novel subtype of dopamine neurons within the mouse substantia nigra. The results show that the neural activity patterns of the genetically identified subtypes map to differing features of locomotion, such as acceleration, deceleration, and appetitive. View original preprint.
Astrocytic LRRK2 controls synaptic connectivity through ERM phosphorylation
By savannah onThis work reveals a causal link between the astrocytic and synaptic dysfunction induced by the PD-linked mutation, LRRK2 G2019S, providing a non-cell autonomous mechanism for rescuing aberrant cortical wiring
Sex distribution of GBA1 variant carriers with dementia with Lewy Bodies and Parkinson’s disease
By savannah onSex distribution of GBA1 variant carriers with dementia with Lewy Bodies and Parkinson's disease.
LRRK2 kinase inhibition reverses G2019S mutation-dependent effects on tau pathology spread
By Emma Sherrell onPreprint: 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.
A topographical atlas of αSyn dosage and cell-type expression in the mouse brain and periphery
By Emma Sherrell onPreprint: 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.
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.