α-Synuclein pathology disrupts mitochondrial function in dopaminergic and cholinergic neurons at-risk in Parkinson’s disease
By Emma Sherrell onThe mechanisms by which intracellular aSYN pathology contributes to dysfunction and degeneration of neurons in the brain are still unclear. Genetic and physiological methods were used to monitor mitochondrial function in substantia nigra pars compacta (SNc) dopaminergic and pedunculopontine nucleus (PPN) cholinergic neurons after stereotaxic injection of aSYN pre-formed fibrils (PFFs) into the mouse brain.
Dynamic behaviour restructuring mediates dopamine-dependent credit assignment
By Emma Sherrell onPublished: Reinforcement mechanism promotes not only reinforcement, but gradual refinement of the entire behavioral repertoire to assign credit to specific actions and action sequences that lead to dopamine release.
Scalable, flexible carbon fiber electrode thread arrays for three-dimensional probing of neurochemical activity in deep brain structures of rodents
By Emma Sherrell onThe authors' CFET array has the potential to unlock a wide range of applications, from uncovering the role of neuromodulators in synaptic plasticity, to addressing critical safety barriers in clinical translation towards diagnostic and adaptive treatment in Parkinson’s disease and major mood disorders.
Synchronous measurements of extracellular action potentials and neurochemical activity with carbon fiber electrodes in nonhuman primates
By Emma Sherrell onSynchronous measures of spike and dopamine signals displayed contrasting relations to the behavioral task parameters, as taken from the small set of representative data, suggesting a complex relationship between these two modes of neural signaling.
Neuropathological assessment of the olfactory bulb and tract in individuals with COVID-19
By Emma Sherrell onThe team concluded from their autopsy series that after a fatal course of COVID-19, microscopic changes, when present, in the rostral, intracranial portion of the olfactory circuitry generally reflected neurodegenerative processes seen elsewhere in the brain. In general, inflammation correlated best with the degree of Alzheimer's-linked tauopathy and declined with progression of age in COVID19+ patients.
Persistent hyposmia as surrogate for α-Synuclein-Linked brain pathology
By Emma Sherrell onPreprint: The team identified significant age- and posit that simple-to-administer, quantitative smell tests could serve as inexpensive screening tools in future population studies for the identification of α-synuclein-related brain disorders, including Parkinson's during its premotor phase.
Response to: “Is Gauchian genotyping of GBA1 variants reliable?”
By Emma Sherrell onPreprint: To understand the cause of these discrepancies, the team reviewed their data, and concluded that they are misinterpreting Gauchian results in 8 of the 11 discrepant samples, and incorrectly using Gauchian to analyze low-coverage 1kGP samples.
Microbial amyloids in neurodegenerative amyloid diseases
By Emma Sherrell onPublished: Inhibiting microbial amyloids or their interactions with the host, may therefore represent a tangible target to limit various amyloid pathologies.
Anionic nanoplastic contaminants promote Parkinson’s disease–associated α-synuclein aggregation
By Emma Sherrell onThese results highlight a potential link for further exploration between nanoplastic pollution and α-synuclein aggregation associated with Parkinson’s disease and related dementias.
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.