Loss of primary cilia and dopaminergic neuroprotection in pathogenic LRRK2-driven and idiopathic Parkinson’s disease
By onActivating LRRK2 mutations causes Parkinson's disease. Here, the data strongly suggest that loss of cilia in specific striatal cell types decreases neuroprotection for dopamine neurons in mice and human Parkinson's disease.
Kufor-Rakeb Syndrome-Associated Psychosis: A Novel Loss-of-Function ATP13A2 Variant and Response to Treatment
By onATP13A2 mutations cause Kufor-Rakeb syndrome, leading to parkinsonism with various neurological symptoms. Quetiapine showed promise in treating associated psychosis with good tolerance, suggesting its potential for managing such cases effectively.
Fluorescence Microscopy Shadow Imaging for Neuroscience
By onThis review highlights the inherent limitations of fluorescence microscopy and conventional labeling and summarizes the pros and cons of recent shadow imaging approaches.
Transcriptional programs mediating neuronal toxicity and altered glial-neuronal signaling in a Drosophila knock-in tauopathy model
By onMutations in gene encoding tau cause autosomal dominant forms of frontotemporal dementia. This article presents a genetic model of tauopathy, which recapitulates the genetic context and phenotypic features of the disease.
Open-Source Platform for Kinematic Analysis of Mouse Forelimb Movement
By onAn open-source behavioral platform and software solution for studying fine motor skills in mice performing reach-to-grasp tasks.
The pathogenesis of Parkinson’s disease
By onThis review is the second in a Series of three papers about Parkinson's disease published in the Lancet. Parkinson's disease is a progressive neurodegenerative condition associated with the deposition of aggregated α-synuclein. Insights into the pathogenesis of Parkinson's disease have been derived from genetics and molecular pathology. Biochemical studies, investigation of transplanted neurons in patients with Parkinson's disease, and cell and animal model studies suggest that abnormal aggregation of α-synuclein and spreading of pathology between the gut, brainstem, and higher brain regions probably underlie the development and progression of Parkinson's disease. At a cellular level, abnormal mitochondrial, lysosomal, and endosomal function can be identified in both monogenic and sporadic Parkinson's disease, suggesting multiple potential treatment approaches. Recent work has also highlighted maladaptive immune and inflammatory responses, possibly triggered in the gut, that accelerate the pathogenesis of Parkinson's disease. Although there are currently no disease-modifying treatments for Parkinson's disease, we now have a solid basis for the development of rational neuroprotective therapies that we hope will halt the progression of this disabling neurological condition.
3D bioprinting of human neural tissues with functional connectivity
By onTeam Scherzer developed a 3D bioprinting platform to assemble tissues with defined human neural cell types in a desired dimension using a commercial bioprinter.
Methods and applications for single-cell and spatial multi-omics
By onIn this Review, we highlight advances in the developing field of single-cell and spatial multi-omics technologies (multimodal omics approaches), and the computational strategies needed to integrate information across these molecular layers.
Comparative analysis of methods to reduce activation signature gene expression in PBMCs
By onPreserving the in vivo cell transcriptome is essential for accurate profiling, yet factors during cell isolation including time ex vivo and temperature induce artifactual gene expression, particularly in stress-responsive immune cells. In this study, we investigated two methods to mitigate ex vivo activation signature gene (ASG) expression in peripheral blood mononuclear cells (PBMCs): transcription and translation inhibitors (TTis) and cold temperatures during isolation. Comparative analysis of PBMCs isolated with TTis revealed reduced ASG expression. However, TTi treatment impaired responsiveness to LPS stimulation in subsequent in vitro experiments. In contrast, cold isolation methods also prevented ASG expression; up to a point where the addition of TTis during cold isolation offered minimal additional advantage. These findings highlight the importance of considering the advantages and drawbacks of different isolation methods to ensure accurate interpretation of PBMC transcriptomic profiles.
Disease progression strikingly differs in research and real-world Parkinson’s populations
By onThis study characterizes Parkinson's progression in diverse populations. It delineates systemic divergences in the patient populations enrolled in research settings vs. patients in the real world.
An open-source MRI compatible frame for multimodal presurgical mapping in macaque and capuchin monkey
By onThe authors developed an MRI-compatible stereotaxic frame for use in various nonhuman primate species to allow precise multimodal alignment without marker implantation. The design files are publicly available to facilitate low-cost manufacturing.
Nova-ST: Nano-Patterned Ultra-Dense platform for spatial transcriptomics
By onNova-ST, a dense nano-patterned spatial transcriptomics technique derived from randomly barcoded Illumina sequencing flow cells enables customized, low-cost, flexible, and high-resolution spatial profiling of large tissue sections.
The VEGFs/VEGFRs system in Alzheimer’s and Parkinson’s diseases: Pathophysiological roles and therapeutic implications
By onThis article focuses on the VEGFs/VEGFRs involvement in neurodegenerative diseases by reviewing the current literature on the rather complex VEGFs/VEGFRs contribution to the pathogenic mechanisms of Alzheimer’s (AD) and Parkinson’s disease (PD).
Integrative analysis reveals a conserved role for the amyloid precursor protein in proteostasis during aging
By onAβ peptides derived from the amyloid precursor protein (APP) have been implicated in Alzheimer’s disease. Results demonstrate a conserved role for APP in controlling age-dependent proteostasis with plausible relevance to Alzheimer’s disease.
Pathways controlling neurotoxicity and proteostasis in mitochondrial complex I deficiency.
By onNeuromuscular disorders caused by dysfunction of the mitochondrial respiratory chain are common, severe and untreatable. We recovered a number of mitochondrial genes, including electron transport chain components, in a large forward genetic screen for mutations causing age-related neurodegeneration in the context of proteostasis dysfunction. We created a model of complex I deficiency in the Drosophila retina to probe the role of protein degradation abnormalities in mitochondrial encephalomyopathies. Using our genetic model, we found that complex I deficiency regulates both the ubiquitin/proteasome and autophagy/lysosome arms of the proteostasis machinery. We further performed an in vivo kinome screen to uncover new and potentially druggable mechanisms contributing to complex I related neurodegeneration and proteostasis failure. Reduction of RIOK kinases and the innate immune signaling kinase pelle prevented neurodegeneration in complex I deficiency animals. Genetically targeting oxidative stress, but not RIOK1 or pelle knockdown, normalized proteostasis markers. Our findings outline distinct pathways controlling neurodegeneration and protein degradation in complex I deficiency and introduce an experimentally facile model in which to study these debilitating and currently treatment-refractory disorders.
Alterations in neurotransmitter co-release in Parkinson’s disease
By onParkinson's disease involves degeneration of dopamine neurons, leading to basal ganglia circuit changes. These neurons also release glutamate and GABA. Understanding co-release dynamics could help identify circuit dysfunction in Parkinson's disease.
Dopamine across timescales and cell types: Relevance for phenotypes in Parkinson’s disease progression
By onDopamine neurons in the SNc are crucial for movement and learning. In Parkinson's Disease, their degeneration leads to various symptoms. Recent research highlights heterogeneity in these neurons, impacting PD progression and treatment development.
Proportion and distribution of neurotransmitter-defined cell types in the ventral tegmental area and substantia nigra pars compacta
By onThis is the most complete anatomical description of transmitter-defined cell types across SNc and VTA to date. Emphasizing the heterogeneity within these dopamine-rich regions, 57% of SNc neurons express glutamate or GABA markers, as do 78% in VTA.
Role of dopamine neuron activity in Parkinson’s disease pathophysiology
By onNeural activity disruptions in neurodegenerative diseases like Parkinson's may occur early. Abnormal dopamine neuron activity in PD could worsen neurotoxic effects, offering insight for future treatments to protect these neurons.
The role of α-synuclein in exocytosis
By onReview focuses on α-synuclein's role in exocytosis, a key process in Parkinson's disease. Despite unclear pathogenesis, evidence points to αsyn's involvement in regulating cellular processes.
