α-Synuclein overexpression and the microbiome shape the gut and brain metabolome in mice
By onThe authors quantitatively profiled nearly 630 metabolites in the gut, plasma and brain of α-synuclein-overexpressing mice with or without associated microbiota, finding tissue-specific changes driven by genotype, microbiome, and their interaction.
SynBot is an open-source image analysis software for automated quantification of synapses
By onSynapses are crucial for brain function. SynBot, an open-source software, automates synapse analysis using advanced algorithms to improve accuracy and reproducibility in studying synaptic phenotypes
Microendoscopic calcium imaging in motor cortices of macaques during rest and movement
By onMotor cortical regions have undergone evolutionary expansion and specialization from rodents to primates. Studying these regions in non-human primates (NHPs) is relevant to understanding motor control in NHP models of movement disorders.
RAB32 Ser71Arg in autosomal dominant Parkinson’s disease: linkage, association, and functional analyses
By onRAB GTPases are regulators and substrates of LRRK2, and variants in the LRRK2 gene are important risk factors for Parkinson's disease. Here, the authors explore genetic variability in RAB GTPases within cases of familial Parkinson's disease.
Loss of the lysosomal lipid flippase ATP10B leads to progressive dopaminergic neurodegeneration and Parkinsonian motor deficits
By onATP10B, a lipid flippase in endosomes/lysosomes, is linked to Parkinson's disease. Knockdown in rats led to motor deficits, reduced dopamine levels, and loss of dopaminergic neurons. Human cell studies supported these findings.
Selective dopaminergic neurotoxicity modulated by inherent cell-type specific neurobiology
By onThis review article focuses on the key biological features of DAergic neurons that increase neurotoxicant susceptibility
Excessive firing of dyskinesia-associated striatal direct pathway neurons is gated by dopamine and excitatory synaptic input
By on-FosTRAP captures striatal neurons activated in levodopa-induced dyskinesia -Levodopa evokes high firing rates in TRAPed direct pathway striatal neurons (dMSNs) -TRAPed dMSNs show enhanced dopamine sensitivity and excitatory synaptic input
Autophagy preferentially degrades non-fibrillar polyQ aggregates.
By onProteins with expanded polyQ repeats form aggregates in neurodegenerative diseases. Autophagy struggles to clear these aggregates due to difficulty interacting with fibrillar structures, suggesting a need for new strategies to improve clearance.
Parkinsonism Sac domain mutation in Synaptojanin-1 affects ciliary properties in iPSC-derived dopaminergic neurons
By onWe show that a mutation in SJ1 that causes early-onset Parkinsonism affects the cilia of iPSC-derived DA neurons. Cilia are longer and show an accumulation of calcium channels and ubiquitinated proteins relative to control neurons, suggesting an effe
Contextual AI models for single-cell protein biology
By onThis study describes PINNACLE a deep learning approach establish context dependent networks. PINNACLE is a key algorithm used in our ASAP project to provide cell type , age-or disease context to our experimental datasets.
Integrating population genetics, stem cell biology and cellular genomics to study complex human diseases
By onThis review describes current state-of-the art of pooled "village-style" hPSC-based assays. This is a major topic for disease modeling including PD and for linking disease with genetic and/or environmental risk and part of our experimental ASAP work.
SARS-CoV-2 infection causes dopaminergic neuron senescence
By onThe ASAP-supported aspect of this study involves the DA neuron senescence work, and experiments using ASAP lines (isogenic a-SYN triplication) to assess interaction of genetic vulnerability with viral-induced senescence as PD penetrance factor.
Genome-wide CRISPR screen identifies neddylation as a regulator of neuronal aging and AD neurodegeneration.
By onWe found that neddylation-inhibition triggers age-related features in PSC-derived neurons for modeling AD or PD. This strategy can induce late-onset phenotypes including degeneration when applied to DA neurons from PD- versus isogenic control PSCs.
PINK1 deficiency rewires early immune responses in a mouse model of Parkinson’s disease triggered by intestinal infection
By onUsing single-cell RNAseq in our PINK KO mouse model, we demonstrate that peripheral myeloid cells are the earliest highly dysregulated immune cell type followed by an aberrant T cell response shortly after infection.
The Gut Microbiota in Parkinson Disease: Interactions with Drugs and Potential for Therapeutic Applications
By onThis article summarises the most up-to-date knowledge in pharmacomicrobiomics in PD, and discusses how the manipulation of gut microbiota represents a potential new therapeutic avenue for PD.
Cortico-basal ganglia plasticity in motor learning
By onThe cortico-basal ganglia circuit is particularly crucial for acquiring and executing motor skills, and neuronal activity in these regions is linked to movement. Here, the authors detail the cortico-basal ganglia plasticity in motor learning
Distinct spatially organized striatum-wide acetylcholine dynamics for the learning and extinction of Pavlovian associations
By onStriatal acetylcholine (ACh) signaling in mice shows opposing changes across different regions, with positive and negative prediction errors encoded in anterior dorsal striatum.
More of less: Novel multi-ome profiling of single human neurons
By onThis review describes a novel single-cell multi-omic method, simultaneously profiling transcriptome, DNA methylome, and chromatin accessibility, to shed light on human neurons.
Biochemical Fractionation of Human α-Synuclein in a Drosophila Model of Synucleinopathies
By onSynucleinopathies involve α-synuclein accumulation in Lewy Bodies. A-synuclein in Drosophila helps understand its effects. A method using detergents and sonication separates soluble/insoluble forms of human α-synuclein from fly brains aiding research
Neither alpha-synuclein fibril strain nor host murine genotype influences seeding efficacy
By onParkinson’s disease (PD) involves motor symptoms and αsyn aggregation. GBA1 mutations may worsen PD progression. Testing showed similar αsyn spread regardless of genotype or αsyn strain, with unique interactions found in GBA-PD brains.
