Proportion and distribution of neurotransmitter-defined cell types in the ventral tegmental area and substantia nigra pars compacta
By Emma Sherrell onThe relative distributions and proportions of neurotransmitter-defined cell types across VTA and SNc have remained unclear. The data shown here complement recent single-cell RNAseq studies and support a more diverse landscape of neurotransmitter-defined cell types in VTA and SNc.
GLP-1 receptor agonism ameliorates Parkinson’s disease through 1 modulation of neuronal insulin signalling and glial suppression
By Emma Sherrell onNeuronal insulin resistance is linked to the pathogenesis of Parkinson's disease through unclear, but potentially targetable, mechanisms. The authors delineated neuronal and glial mechanisms of insulin resistance and glucagon-like 1 peptide (GLP-1) receptor agonism in human iPSC models of synucleinopathy.
Adoptive transfer of mitochondrial antigen-specific CD8+ T-cells in mice causes parkinsonism and compromises the dopamine system
By Emma Sherrell onThe degeneration of dopamine neurons in the ventral midbrain is linked to the development of motor symptoms in Parkinson's disease (PD). Evidence suggests that neuroinflammation and mitochondrial dysfunction drive neurodegenerative mechanisms in PD. Results provide evidence for mitochondrial-specific CD8+ T cell infiltration in the brain in driving PD-like pathology.
LRRK2 G2019S mutation suppresses differentiation of Th9 and Treg cells via JAK/STAT3
By Emma Sherrell onThe Leucine-rich repeat kinase-2 (LRRK2) G2019S mutation is one of the well-recognized genetic risk factors in Parkinson's disease (PD). Increased LRRK2 activity was also observed in immune cells from PD patients. The authors generated and characterized a new T cell receptor (TCR) transgenic mouse strain bearing LRRK2 G2019S knock-in mutation.
Deep sequencing of proteotoxicity modifier genes uncovers a Presenilin-2/beta-amyloid-actin genetic risk module shared among alpha-synucleinopathies
By Emma Sherrell onConventional genetic analyses are underpowered to address whether neurodegenerative diseases linked to misfolding of the same protein share genetic risk drivers or whether different protein-aggregation pathologies in neurodegeneration are mechanistically related. The authors study patients based on protein aggregation phenotype to detect variants in a targeted set of genes.
Alpha-synuclein aggregates trigger anti-viral immune pathways and RNA editing in human astrocytes
By Emma Sherrell onParkinson's disease is a neurodegenerative disease characterized by a proteinopathy with marked astrogliosis. To investigate how a proteinopathy may induce a reactive astrocyte state, and the consequence of reactive astrocytic states on neurons, the authors generated hiPSC-derived astrocytes, neurons, and co-cultures and exposed them to small soluble alpha-synuclein aggregates.
Dopamine neuron activity encodes the length of upcoming contralateral movement sequences
By Emma Sherrell onThe relationship between the activity of dopaminergic neurons (DANs) and the length of movement sequences is unknown. The authors imaged the activity of SNc DANs in mice. Results indicate that movement-initiation DANs encode more than a general motivation signal and invigorate aspects of contralateral movements. View original preprint.
Oncogenic BRAF V600E induces glial proliferation through ERK and neuronal death through JNK
By Emma Sherrell onActivating V600E in BRAF is a common driver mutation in cancers of multiple tissue origins. BRAF V600E has also been implicated in neurodegeneration. The present study aims to characterize BRAF V600E on cell death and survival in three major cell types of the CNS: neurons, astrocytes, and microglia.
Integrative analysis reveals a conserved role for the amyloid precursor protein in proteostasis during aging
By Emma Sherrell onAβ peptides derived from the amyloid precursor protein (APP) have been implicated in the pathogenesis of Alzheimer’s disease. However, the normal function of APP is less clear. Results demonstrate a conserved role for APP in controlling age-dependent proteostasis with plausible relevance to Alzheimer’s disease.
Modeling gene-environment interactions in Parkinson’s disease: Helicobacter pylori infection of Pink1-/- mice induces CD8 T cell-dependent motor and cognitive dysfunction
By Emma Sherrell onParkinson's disease (PD) is a neurodegenerative disorder characterized by loss of motor function. Using a mouse model, the authors demonstrate that infection with Helicobacter pylori leads to the development of motor and cognitive signs.
Large-scale visualization of α-synuclein oligomers in Parkinson’s disease brain tissue
By Emma Sherrell onParkinson’s disease is a neurodegenerative condition characterized by large intraneuronal aggregates in the brain. It has been hypothesized that these large aggregates may form from smaller soluble protein assemblies, often termed oligomers. ASA-PD, is a new imaging method to generate large-scale α-synuclein oligomer maps in post-mortem human brain tissue.
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.