The VEGFs/VEGFRs system in Alzheimer’s and Parkinson’s diseases: Pathophysiological roles and therapeutic implications
By Emma Sherrell 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).
Nova-ST: Nano-patterned ultra-dense platform for spatial transcriptomics
By Emma Sherrell onExisting spatial transcriptomics techniques are either limited by capture array density or are cost-prohibitive for large-scale atlasing. Nova-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.
An open-source MRI-compatible frame for multimodal presurgical mapping in macaque and capuchin monkey
By Emma Sherrell onNeurosurgical targeting in nonhuman primates (NHPs) requires presurgical anatomy mapping with neuroimaging techniques (MRI, CT, PET). Given the varied tissue contrasts that these imaging techniques produce, the alignment of imaging-based coordinates to surgical apparatus can be cumbersome. The authors developed an MRI-compatible stereotaxis that allows alignment through technique-specific fiducial markers.
Disease progression strikingly differs in research and real-world Parkinson’s populations
By Emma Sherrell onCharacterization of Parkinson's disease (PD) progression using real-world evidence could guide clinical trial design and identify subpopulations. This 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.
iSCORE-PD: an isogenic stem cell collection to research Parkinson’s disease
By Emma Sherrell onGenome-edited human pluripotent stem cells (hPSCs) offer the unique potential to advance the understanding of Parksion's etiology by providing disease-relevant cell types carrying patient mutations along with isogenic control cells. To facilitate this experimental approach, the authors generated a collection of cell lines harboring mutations in genes associated with Parkinson's.
Methods and applications for single-cell and spatial multi-omics
By Emma Sherrell onIn this review, the authors highlight advances in the fast-developing field of single-cell and spatial multi-omics technologies (also known as multimodal omics approaches), and the computational strategies needed to integrate information across molecular layers.
The pathogenesis of Parkinson’s disease
By Emma Sherrell onThis review is the second in a series of three papers about Parkinson's disease published in the Lancet.
Systemic inflammation triggers long-lasting neuroinflammation and accelerates neurodegeneration in a rat model of Parkinson’s disease overexpressing human alpha-synuclein
By Julia Julia Leonard onIncreasing efforts have been made to elucidate how genetic and environmental factors interact in Parkinson's disease (PD). In the present study, the authors assessed the development of PD-like symptoms on a PD rat model overexpressing human α-synuclein at a presymptomatic age, exposed to a pro-inflammatory insult by injection of lipopolysaccharide.
Kufor-Rakeb Syndrome-Associated Psychosis: A novel loss-of-function ATP13A2 variant and response to treatment
By Julia Julia Leonard onBiallelic (autosomal recessive) pathogenic variants in ATP13A2 cause a form of juvenile-onset parkinsonism, termed Kufor-Rakeb syndrome. The article describes the treatment response in an individual with Kufor-Rakeb syndrome-associated psychosis.
Toward a standard model for autophagosome biogenesis
By Emma Sherrell onTwo papers in this issue resolve a long-standing obstacle to a “standard model” for autophagosome biogenesis in mammals.
The annotation and function of the Parkinson’s and Gaucher disease-linked gene GBA1 has been concealed by its protein-coding pseudogene GBAP1
By Emma Sherrell onHere, the authors identify novel transcripts from both GBA1 and GBAP1, including protein-coding transcripts that are translated in vitro and detected in proteomic data, but that lack GCase activity.
Central and peripheral innate and adaptive immunity in Parkinson’s disease
By Emma Sherrell onParkinson’s disease (PD) is a multisystem disorder with characteristics of a chronic inflammatory disease. To develop effective immunomodulatory interventions to combat PD, researchers need to think innovatively about the implications of orchestrated central and peripheral innate and adaptive immune responses that occur as the disease begins and progresses.
Pathways controlling neurotoxicity and proteostasis in mitochondrial complex I deficiency
By Julia Julia Leonard onNeuromuscular disorders caused by dysfunction of the mitochondrial respiratory chain are common, severe, and untreatable. The authors 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.
Loss of primary cilia and dopaminergic neuroprotection in pathogenic LRRK2-driven and idiopathic Parkinson’s disease
By Julia Julia Leonard onActivating LRRK2 mutations causes Parkinson's disease. Previously, work showed that cholinergic interneurons and astrocytes lose primary cilia in LRRK2 mutant mice. 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.
Open-source platform for kinematic analysis of mouse forelimb movement
By Emma Sherrell onAn open-source behavioral platform and software solution for studying fine motor skills in mice performing reach-to-grasp tasks. The behavioral platform uses readily available and 3D-printed components and was designed to be affordable and universally reproducible.
3D bioprinting of human neural tissues with functional connectivity
By Emma Sherrell onProbing how human neural networks operate is hindered by the lack of reliable human neural tissues amenable to the dynamic functional assessment of neural circuits. Team Scherzer developed a 3D bioprinting platform to assemble tissues with defined human neural cell types in a desired dimension using a commercial bioprinter.
Visualizing chaperone-mediated multistep assembly of the human 20S proteasome
By Emma Sherrell onDedicated assembly factors orchestrate the stepwise production of molecular machines, including the 28-subunit proteasome core particle (CP) that mediates protein degradation. This article presents cryo-EM reconstructions of seven recombinant human subcomplexes that visualize all five chaperones and the three active site propeptides across a wide swath of the assembly pathway.
Polyglucosan body density in the aged mouse hippocampus is controlled by a novel modifier locus on chromosome 1
By Emma Sherrell onAging can be associated with the accumulation of polyglucosan bodies (PGBs). While PGBs have a detrimental effect on cognition, the underlying mechanism and clinical relevance of age-related PGB accumulation remain unknown. Here, the authors investigated the genetic basis and functional impact of age-related PGB accumulation in mice.
Transcriptional programs mediating neuronal toxicity and altered glial-neuronal signaling in a Drosophila knock-in tauopathy model
By Emma Sherrell onMutations in the gene encoding tau cause autosomal dominant forms of frontotemporal dementia. Prior models of frontotemporal dementia replicate features of the disease but do not recreate the genetic context. This article presents a genetic model of tauopathy, which recapitulates the genetic context and phenotypic features of the disease.
Neuronal dysfunction and gene modulation by non-coding RNA in Parkinson’s disease and synucleinopathies
By Julia Julia Leonard onEmerging evidence suggests that non-coding RNAs (ncRNAs) contribute to molecular events underlying progressive neuronal degeneration. This review discusses recent literature focused on the role of RNA-based mechanisms involved in different aspects of neuronal pathology in Parkinson’s disease and synucleinopathy models.