Genetically Encoded and Modular SubCellular Organelle Probes (GEM SCOPe) reveal lysosomal and mitochondrial dysfunction driven by PRKN
By onLysosomal and mitochondrial dysfunction are implicated in many diseases. GEM-SCOPe, a modular toolbox of fluorescent markers, helps visualize these organelles. In a PRKN-knockout model of PD, GEM-SCOPe identified disease-associated changes.
Development of a Simplified Smell Test to Identify Patients with Typical Parkinson’s as Informed by Multiple Cohorts, Machine Learning and External Validation
By onReduced olfaction is a common feature of typical Parkinson disease (PD) and dementia with Lewy bodies (DLB). We have created a simplified smell test based on seven specific odorants that can distinguish PD/DLB patients from healthy controls.
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,
GEARBOCS: An Adeno Associated Virus Tool for In Vivo Gene Editing in Astrocytes
By onGEARBOCS is a non-invasive method for precise gene editing in astrocytes using CRISPR/Cas9. It allows knockout, tagging, and reporter knock-in strategies, revealing the roles of Sparcl1 and Vamp2 in synapse maintenance in the mouse visual cortex.
Functional efficacy of the MAO-B inhibitor safinamide in murine substantia nigra pars compacta dopaminergic neurons in vitro: a comparative study with tranylcypromine
By onSafinamide (SAF) is used for PD by enhancing dopamine signal. SAF prolongs recovery from dopamine-mediated firing inhibition in SNpc DAergic neurons, mildly compared to tranylcypromine, suggesting multiple sites of action for SAF's therapeutics.
The Role of Alpha-Synuclein Pathology
By onAlpha-Synuclein (aSyn) is key protein in PD and other synucleinopathies, causing neurodegeneration. Despite its importance, there is a lack of consensus on markers to define aSyn aggregates, highlighting the need for better research tools and models.
Peripheral Blood Immune Cells from Individuals with Parkinson’s Disease or Inflammatory Bowel Disease Share Deficits in Iron Storage and Transport that are Modulated by Non-Steroidal Anti-Inflammatory Drugs
By onParkinson's (PD) involves dysregulated neuroimmune crosstalk and gut-brain axis inflammation. Gastrointestinal dysfunction is a common early symptom. Iron dysregulation and immune cell dysfunction may play a role, with shared features in PD an IBD.
Behavioral screening defines three molecular Parkinsonism 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.
Microbiome-based biomarkers to guide personalized microbiome-based therapies for Parkinson’s disease
By onAddressing biomarkers in PD, researchers propose using the gut microbiome to guide patient selection for clinical trials. By identifying dysbiotic features, they aim to personalize treatments and improve success rates in disease-modifying therapies.
Reconstitution of BNIP3/NIX-mediated autophagy reveals two pathways and hierarchical flexibility of the initiation machinery
By onDuring selective autophagy transmembrane cargo receptors can trigger autophagy by recruiting different complexes and utilizing multiple pathways. This flexibility in autophagy initiation has important therapeutic implications.
Cortico-amygdala synaptic structural abnormalities produced by templated aggregation of α-synuclein
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.
Dissociation of putative open loop circuit from ventral putamen to motor cortical areas in humans I: high-resolution connectomics
By onHigh-resolution connectomics in human participants provides evidence for a non-canonical circuit linking the limbic ventral putamen to the motor cortex. These data are in line with previous findings in nonhuman primates.
Movement-related activity in the internal globus pallidus of the parkinsonian macaque
By onThis study of MPTP-induced parkinsonism in macaques indicates that changes in the timing of task-related neural activity of the internal segment of the globus pallidus (GPi) correlate with the severity of motor impairments.
Temporal control of acute protein aggregate turnover by UBE3C and NRF1-dependent proteasomal pathways
By onNeurodegenerative diseases involve proteostasis loss and protein aggregation leading to cell toxicity. Study reveals proteasome-dependent degradation of misfolded proteins, regulated by NRF1, UBE3C, and RPN13, impacting proteostasis in cells.
CHCHD2 mutant mice display mitochondrial protein accumulation and disrupted energy metabolism
By onMutations in mitochondrial protein CHCHD2 lead to a form of Parkinson's disease. CHCHD2 T61I mutant mice show molecular changes in the brain, altered metabolism favoring glycolysis, and disrupted mitochondrial function in dopamine neurons.
Vibrational Control of Complex Networks
By onComplex networks' stability is crucial, but real-time control can be challenging. This paper proposes using vibrational control on network edges instead of nodes to stabilize systems, providing graph-theoretic conditions and effective design methods.
Parkinson’s Families Project: a UK-wide study of early onset and familial Parkinson’s disease
By onThe genetic variations in familial and early-onset Parkinson’s disease were studied. Most early-onset and familial PD cases do not have a known genetic cause, indicating that there are likely to be further monogenic causes for PD.
Progressive vulnerability of cortical synapses in α-synucleinopathy
By onα-Synuclein aggregation is linked to progressive loss of intracortical VGLUT1+ excitatory synapses, spares VGLUT2+ long-range synapses, and impairs cortical excitatory transmission.
Presynapses are mitophagy pit stops that prevent axon degeneration
By onDefective neuronal mitophagy is linked to PD. Damaged axonal mitochondria accumulate at presynapses, sites of mitophagy initiation and autophagosome formation. of receptor mediated mitophagy with Roxadustat, reveals a potential therapeutic avenue.
Comparative Analysis of AAV Serotypes for Transduction of Olfactory Sensory Neurons
By onThis study compared the efficacy and selectivity of 11 different AAV serotypes for the efficient and selective transduction of murine olfactory sensory neurons in vivo. The findings inform research approaches and gene therapy based initiatives.
