Article Archive

Published: The authors examined the impact of gene variants on mortality and cognitive impairment in PD. Only the non-Gaucher disease causing GBA PD risk variant E326K, of the known PD risk variants, was associated with progression in PD. View original preprint. 

Published: The data available in this repository can be used to replicate all the figures in the authors’ manuscript using their data analysis tutorial available here: https://github.com/aertslab/hydrop_data_analysis. View original preprint.

Leucine-rich-repeat-kinase 1 (LRRK1) and its homologue LRRK2 are multidomain kinases possessing a ROC-CORA-CORB containing GTPase domain and phosphorylate distinct Rab proteins. LRRK1 loss of function mutations cause the bone disorder osteosclerotic metaphyseal dysplasia, whereas LRRK2 missense mutations that enhance kinase activity cause PD. Here, the authors study the mechanism controlling LRRK1 activity and reveal a novel unexpected activation mechanism. View preprint.

Two Parkinson's disease candidate genes, KAT8 and KANSL1, identified through genome-wide studies and a PINK1-mitophagy screen, encode part of the histone acetylating non-specific lethal complex. Here, the authors sought to identify whether the non-specific lethal complex has potential regulatory relationships with other genes associated with Parkinson's disease in human brain.

The enteric nervous system (ENS) integrates cues from the brain and from local signals in the gut to coordinate responses that shape the intestinal milieu. Here, the authors examine the role of neurons in modulating intestinal physiology, mucosal immunity, and gut microbiome structure.

Viewpoint article on CRISPR/Cas9-based functional genomics in human induced pluripotent stem cell–derived models.

Review: Selective autophagy represents a major pathway for the degradation of cargo material. The authors review recent insights into the mechanisms of action of cargo receptors in selective autophagy by focusing on the roles of sequestosome-like cargo receptors in the degradation of misfolded, ubiquitinated proteins and damaged mitochondria.  

Published: Intracellular inclusions accompanying neurodegeneration are histopathologically and ultrastructurally heterogeneous but the significance of this heterogeneity is unclear. iPSC models do not form inclusions in a reasonable timeframe and suffer from limited tractability. The authors developed an iPSC toolbox utilizing piggyBac-based or targeted transgenes to rapidly induce CNS cells with concomitant expression of aggregation-prone proteins. View original preprint.

Published: Phosphorylation of α-synuclein at the Serine-129 site (α-syn Ser129P) is an established pathologic hallmark of synucleinopathies and also a therapeutic target. Exploring AlphaFold2-driven modeling and membrane-binding simulations, the authors offer a new conceptual platform for investigating the role of Ser129 in synucleinopathies, with implications for drug development. View original preprint. View original preprint.  

Preprint: Cells acquire the polyamines putrescine (PUT), spermidine (SPD), and spermine (SPM) via the complementary action of polyamine uptake and synthesis pathways. The endosomal P5B-type ATPases ATP13A2 and ATP13A3 emerge as major determinants of mammalian polyamine uptake. Our biochemical evidence shows that fluorescently labeled polyamines are genuine substrates of ATP13A2.  

Published: Traditional methods are too slow to preserve the labile Golgi metabolome and transient protein interactions. Here, the authors develop a method for the rapid capture of intact Golgi from human cells via Golgi immunoprecipitation (Golgi-IP). Using high-resolution mass spectrometry, the approach allows the unbiased characterization of the Golgi proteome, metabolome, and lipidome.  

Preprint: The authors use orthogonal proteomic strategies to provide a global molecular inventory of autophagic cargo during nutrient stress in mammalian cell lines. Through prioritization of autophagic cargo, we identify a heterodimeric pair of membrane-embedded proteins, YIPF3 and YIPF4, as receptors for Golgiphagy.  

Preprint: 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.

Review: 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.  

Published: 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.

Review: 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.  

Review: 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.

Published: 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.  

Review: 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.  

Review: 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.