Sex-specific microglial responses to glucocerebrosidase inhibition: relevance to GBA1-linked Parkinson’s disease
By savannah onPreprint: To elucidate the impact of sex-specific microglia heterogenicity to the susceptibility of neuronal stress, the authors analyzed the dynamic changes in shape and motility occurring in primary mouse microglia following pro-inflammatory or neurotoxic insults, thus finding sex-specific responses of microglial subpopulations.
More of less: novel multi-ome profiling of single human neurons
By savannah onReview: Epigenetic modifications to DNA and chromatin interact to influence gene expression and cellular phenotypes, but defining these omics layers in complex tissues is a daunting task. In this issue of Cell Genomics, Luo et al. describe a novel single-cell multi-omic method, simultaneously profiling transcriptome, DNA methylome, and chromatin accessibility, to shed light on human neurons.
Deficiency of the frontotemporal dementia gene GRN results in gangliosidosis
By savannah onPublished: Here, the authors discover that PGRN-deficient human cells and murine brains, as well as human frontal lobes from GRN-mutation FTD patients have increased levels of gangliosides, glycosphingolipids that contain sialic acid. Lysosomal ganglioside accumulation may contribute to neuroinflammation and neurodegeneration susceptibility observed in FTD due to PGRN deficiency and other neurodegenerative diseases.
Gut microbiome-mediated regulation of neuroinflammation
By savannah onReview: The intestinal microbiome influences neuroinflammatory disease in animal models, and recent studies have identified multiple pathways of communication between the gut and brain. As preclinical research findings and concepts are applied to humans, the potential impacts of the gut microbiome – brain axis on neuroinflammation represent exciting frontiers for further investigation.
Bile acids and neurological disease
By savannah onReview: This review focuses on how bile acids are being used in clinical trials to treat neurological diseases due to their central involvement with the gut-liver-brain axis and their physiological and pathophysiological roles in both normal brain function and multiple neurological diseases.
Multiple genome alignment in the telomere-to-telomere assembly era
By savannah onPublished: This review provides an overview of the algorithmic template that most multiple genome alignment methods follow. We also discuss prospective areas of improvement of multiple genome alignment for keeping up with continuously arriving high-quality T2T assembled genomes and for unlocking clinically-relevant insights.
Interactions of dopamine, iron, and alpha-synuclein linked to dopaminergic neuron vulnerability in Parkinson’s disease and Neurodegeneration with Brain Iron Accumulation disorders
By savannah onReview: This review analyzes the involvement of disrupted dopamine, alpha-synuclein, and iron pathways in dopamine neuron physiology and function, and discusses how disrupted interplay of dopamine, alpha-synuclein, and iron pathways may synergize to promote pathology and drive the unique vulnerability to disease states.
Neuronal presentation of antigen and its possible role in Parkinson’s disease
By savannah onReview: Patients with Parkinson's disease and other synucleinopathies often exhibit autoimmune features, including CD4+ and some CD8+ T lymphocytes that recognize epitopes derived from alpha-synuclein. This article reviews the literature on neuronal antigen presentation and its potential role in PD.
Induced pluripotent stem cells: a tool for modeling Parkinson’s disease
By savannah onReview: Recent advances in induced pluripotent stem cell (iPSC) technology have made it possible to generate patient-derived DA neuronal cell culture and organoid models of PD. These models have contributed to understanding disease mechanisms and the identification of novel targets and therapeutic candidates.
Targeting cellular senescence with senotherapeutics: senolytics and senomorphics
By savannah onReview: This article reviews the current state of the development of senolytics and senomorphics for the treatment of age-related diseases and disorders and extension of healthy longevity. In addition, the challenges of documenting senolytic and senomorphic activity in pre-clinical models and the current state of the clinical application of the different senotherapeutics are discussed.
State-of-the-art review of the clinical research on menopause and hormone replacement therapy association with Parkinson’s disease: what meta-analysis studies cannot tell us
By savannah onReview: This article provides a unified overview of the clinical literature on the influence of menopause and ovarian hormones on Parkinson’s disease. We highlight the possible sources of conflicting evidence and gather considerations for future observational clinical studies that aim to explore the neurological impact of menopause-related features in Parkinson’s disease.
Molecular heterogeneity in the substantia nigra: a roadmap for understanding PD motor pathophysiology
By savannah onReview: This article discusses the existing knowledge of DA neuron subtypes and attempts to provide a roadmap for how their distinctive properties can provide novel insights into the motor symptoms of Parkinson's disease (PD).
Sst+ GPi output neurons provide direct feedback to key nodes of the basal ganglia and drive behavioral flexibility
By savannah onPreprint: The GPi-LHb pathway is the main output of the basal ganglia suggested to shape motivated behaviors. Here, the authors propose that GPi Sst+ neurons drive behavioral flexibility through a direct feedback signal to balance the activity of key nodes in the basal ganglia.
Macroscopic dynamics of neural networks with heterogeneous spiking thresholds
By savannah onPublished: The authors develop a new computational model to represent different neuron types and spiking dynamics. The model is comprised of biophysical state variables and parameters, incorporates realistic spike resetting conditions, and accounts for heterogeneity in neural spiking thresholds. These features allow for a broad applicability of the model as well as for a direct comparison to experimental data. View original preprint.
Neural heterogeneity controls computations in spiking neural networks
By savannah onPublished: The authors want to understand how neural heterogeneity affect macroscopic neural dynamics and contribute to neurodynamic functions. Here, the authors study the macroscopic dynamics of networks of heterogeneous Izhikevich neurons. Their analysis suggests that the level of heterogeneity of inhibitory populations controls resonance and hysteresis properties of systems of coupled excitatory and inhibitory neurons. View original preprint.
Temporal landscape of mitochondrial proteostasis governed by the UPRmt
By savannah onPreprint: Breakdown of mitochondrial proteostasis activates quality control pathways including the mitochondrial unfolded protein response (UPRmt) and PINK1/Parkin mitophagy. The authors developed a functional proteomics framework, termed MitoPQ (Mitochondrial Proteostasis Quantification), to dissect the UPRmts role in maintaining proteostasis during stress.
GRN mutations are associated with Lewy body dementia
By savannah onPublished: This paper sought to assess a Lewy body dementia case control cohort for pathogenic variants in GRN and identify mutations among patients.
Assessing the relationship between monoallelic PRKN mutations and Parkinson’s risk
By savannah onPublished: This paper examines the role of heterozygous Parkin mutations in three large independent case control cohorts.
Analysis of Y chromosome haplogroups in Parkinson’s disease
By savannah onPublished: This paper explores the role of the Y chromosome in PD by analyzing whole genome sequencing data from multiple sources.
Deficiency in endocannabinoid synthase 1 DAGLB contributes to Parkinson’s disease and dopaminergic neuron dysfunction
By savannah onPublished: In this paper, the authors linked multiple homozygous loss-of-function mutations in the endocannabinoid 2-AG synthase diacylglcerol lipase beta (DAGLB) to early onset autosomal recessive PD using genetic knockdown and pharmacological inhibition of 2-AG in substantia nigra dopaminergic neurons.
