Structural remodeling of the mitochondrial protein biogenesis machinery under proteostatic stress
By onCryo-ET showed protein aggregates, altered cristae, and reduced ribosome complexes in stressed mitochondria. Mitochondrial Hsp60 undergoes conformational changes to aid in protein folding, shedding light on mitochondrial proteostasis mechanisms.
ATP13A4 gates extracellular polyamine levels to control excitatory synaptogenesis
By onPolyamines are crucial for brain function. ATP13A4 is the main polyamine transporter in astrocytes, impacting astrocyte morphology, synapse formation, and neurodevelopment. Mutations in ATP13A4 are linked to neurodevelopmental disorders.
Mechanisms and clinical implications of gut-brain interactions
By onResearch in the past decade has shed light on the gut-brain connection, revealing its role in disease and therapeutics. Targeting gut-brain pathways shows promise for therapeutic benefits.
Regulator of G protein signaling 10: a critical regulator of chronic systemic inflammation in parkinson’s disease
By onThe inflammatory response must be regulated to avoid chronic systemic inflammation. Imbalance can lead to diseases like Parkinson's. The review explores the link between inflammation, Parkinson's, and the role of RGS10 in regulating inflammation.
Incentive valence differentially engages open- and closed-loop basal ganglia circuits during movement initiation
By onThis study used neuroimaging to show a ventral putamen-centered open-loop circuit linking emotions and movement in humans. Contextual incentives influence which motor circuit is activated, shedding light on paradoxical kinesia in Parkinson's Disease.
Extracellular space diffusion modelling identifies distinct functional advantages of archetypical glutamatergic and GABAergic synapse geometries
By onWe modelled extracellular diffusion in super-resolved images of live brain tissue neuropil. We found that extracellular space geometry shapes local diffusion and this has functional implications for signaling arising from synaptic spill-over.
Protocol for efficient CRISPRi-mediated silencing of retrotransposons in human pluripotent stem cells
By onThis methods paper outlines silencing transposable elements in hiPSCs using CRISPRi. Describes gRNA design, validation via multiome approach. Enables functional studies on TE transcription in hiPSC models.
State-dependent modulation of spiny projection neurons controls levodopa-induced dyskinesia in a mouse model of Parkinson’s disease
By onLID is poorly understood, our research on dyskinetic mice show SPNs' properties oscillate during LID and are influenced by dopamine and acetylcholine signaling. Targeting M1 receptors in iSPNs reduced LID severity and improved levodopa effects.
Excitatory synaptic structural abnormalities produced by templated aggregation of α-syn in the basolateral amygdala
By onPD and DLB involve α-syn inclusions in the amygdala affecting cognition and emotions. Cortico-amygdala synapses with α-syn aggregates show increased volume of synapses, potentially contributing to behavioral impairments.
CREsted: modeling genomic and synthetic cell-type-specific enhancers across tissues and species
By onCREsted, a sequence-based deep learning model, analyzes genomic regulatory code, decodes enhancer grammar, and designs synthetic enhancers. It preprocesses single-cell data, models chromatin accessibility, and compares cell states across tissues.
A single Citrobacter rodentium infection in Pink1 knockout and wild type mice leads to regional blood-brain-barrier perturbation and limited microglial activation without dopamine neuron axon terminal loss
By onResearch suggests immune system activation may contribute to Parkinson’s disease development. Mild infections can increase BBB permeability, triggering brain inflammation in genetically susceptible individuals, potentially leading to PD pathology.
STING dampens the unfolded protein response to enable the presentation of self antigens on MHC-I during inflammation
By onSTING pathway regulates antigen presentation through the UPR, impacting immune response in PD and autoimmune diseases. Targeting STING and UPR could be therapeutic.
An LRRK2 variant blocks NCOA4 trafficking upon iron overload, leading to ferroptotic death
By onWe examined the impact of mutant LRRK2-G2019S on iron homeostasis within a model macrophage cell line. Results revealed a dysregulation of iron-related proteins in steady state and a complete block in the degradation of the ferritinophagy NCOA4.
Cryo-EM structure of soluble VPS13C suggests its regulation by a conformational switch and by calmodulin
By onStructural studies of the Parkinson's protein VPS13C provide a molecular basis for understanding its function and regulation.
Cell-autonomous and non-cell-autonomous drivers of dopamine neuron vulnerability in Parkinson’s disease
By onThis review examines evidence for cell-autonomous mechanisms and non-cell-autonomous processes arising from glial and peripheral immune cells and how these pathways can converge to create chronic cellular stress and trigger cell death mechanisms.
Behavioral screening defines the molecular Parkinsonism-related subgroups in Drosophila
By onWe created a new collection of 24 genetically well-controlled Drosophila models of familial forms of parkinsonism. Using unbiased behavioral screening and machine learning we identified three clusters of mutants that converge.
Selective loss of Primary Cilia and Neurotrophic Signaling in G51D α-Synuclein Mice Highlights a Common Pathway to Parkinson’s Disease
By onG51D α-synuclein mice mimic disease symptoms, showing cilia loss in specific neurons and impaired neurotrophic signaling, contributing to disease progression. This highlights the role of ciliary dysfunction in Parkinson’s.
A RAB7A Phosphoswitch Coordinates Rubicon Homology Protein Regulation of PINK1/Parkin-Dependent Mitophagy
By onPublished: Structural and functional data support a model in which the TBK1-dependent phosphorylation of RAB7A serves as a switch, promoting mitophagy by relieving Rubicon inhibition and favoring Pacer activation. View original preprint.
Adult-specific Reelin expression alters striatal neuronal organization: implications for neuropsychiatric disorders
By onReelin levels might modulate the numbers of striatal interneurons and the density of the nigrostriatal dopaminergic projections, suggesting that these changes may be involved in the protection of Reelin against neuropsychiatric disorders.
Integrated multi-cohort analysis of the Parkinson’s disease gut metagenome
By onThe authors perform metagenomic sequencing of multiple geographically-disparate cohorts and find that stereotypic changes in the functional metabolic potential of the gut microbiome are a consistent feature of PD.
