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.
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.
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.
Activation of transposable elements is linked to a region- and cell-type-specific interferon response in Parkinson’s disease
By onStudy explores transposable elements role in Parkinson's disease neuroinflammation. TE activation in specific brain regions correlates with innate immune responses, indicating potential involvement in chronic neuroinflammation and PD progression.
Robust analytical methods for bis(monoacylglycero)phosphate profiling in health and disease
By onBMP is a crucial phospholipid in lysosomes, impacting metabolic balance and linked to neurodegenerative diseases. LC-MS methods are detailed for accurate BMP analysis, utilizing structural differences and a new CLN5 function for profiling.
Integrated Representations of Threat and Controllability in the Lateral Frontal Pole
By onEmotions can strongly influence behavior, as seen in PD paradoxical kinesia. Here, we demonstrate that anticipating threats enhances motor accuracy through interactions between the amygdala and the anterior pole of the lateral prefrontal cortex.
Evaluating single-cell ATAC-seq atlasing technologies using sequence-to-function modeling
By onSingle-cell chromatin accessibility atlases aid in training deep learning models to decode enhancer logic. HyDrop v2 improves scATAC-seq for training, showing cell numbers can compensate for lower fragment counts.
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.
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.
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.
Experimental and Computational Methods for Allelic Imbalance Analysis from Single-Nucleus RNA-seq Data
By onWe systematically investigated experimental and computational design choices for their effects on allelic imbalance analysis in droplet-based snRNA-seq data from human samples. We show that many factors, including read length, sequencing technology,
Astrocytes mediate the dopaminergic modulation of tonic GABAergic signaling in substantia nigra
By onTo characterize the actions of dopamine on substantia nigra pars reticulata (SNr) GABAergic neurons, optogenetic and electrophysiological tools were used in ex vivo mouse brain slices to monitor synaptic transmission arising from neurons.
5-HT4 Receptor Ligand RS67333 Modulates Striatal Acetylcholine and Dopamine Release via the Inhibition of Acetylcholinesterase
By onThe 5-HT4R agonist RS67333 modulates striatal acetylcholine and dopamine release through acetylcholinesterase inhibition, not 5-HT4R activation, highlighting its potential as an AChE inhibitor for brain disorders.
A Pressure Relief Valve for Lysosomes
By onStudy uncovers a rapid cellular response using TMEM63A-dependent ion efflux to relieve lysosomal membrane tension, preventing failure and allowing slower repair mechanisms to engage.
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.
A human lysosomal storage disorder toolkit for decoding proteome landscapes in cortical and dopaminergic-like induced neurons
By onLysosomal Storage Disorders impact lysosomal function and can be linked to Parkinson's Disease risk. LSD mutant cells show varied endolysosomal proteomes, with specific disruptions in neuronal cells.
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.
Health phenome of Parkinson’s patients reveals prominent mood-sleep cluster
By onIn 933 PD cases vs 291 controls, mood/sleep disorders (depression, anxiety, apnea, RLS) were more common and clustered. Pesticides and head trauma raised odds; smoking lowered. 43% of PD had a mood/sleep disorder.
