Article Archive

The secretion of endogenous α-syn mediated by DNAJC5 is also found in a human neuroblastoma cell line, SH-SY5Y, differentiated into neurons in the presence of retinoic acid, and in human-induced pluripotent stem cell-derived midbrain dopamine neurons. We propose that DNAJC5 forms a palmitoylated oligomer to accommodate and export α-syn.

By normalizing the open science and compliance process across funding bodies, we hope to simplify and streamline researcher, institutional, and funder workflows, allowing researchers to focus on science by easily leveraging resources and building upon the work of others.

Published: The data supports a model in which Rab12 binding to a new site in the LRRK2 Armadillo domain activates LRRK2 kinase for Rab phosphorylation and could serve as a new therapeutic target for a novel class of LRRK2 inhibitors that do not target the kinase domain. View original preprint.

Glucocerebrosidase, a Parkinson´s disease-associated protein, is imported into mitochondria and regulates complex I assembly and function. Collection of protocols for paper: "Glucocerebrosidase, a Parkinson´s disease-associated protein, is imported into mitochondria and regulates complex I assembly and function."  

A bioinformatics approach was taken to investigate the proteome of the NSL complex, to unpick its relevance to PD progression. The authors’ data points to NSL complex members OGT and WDR5 as key drivers of this increased PD association. These findings strengthen a role for mitochondrial quality control in both familial and sporadic disease.

This Blueprint presents initial findings on how ASAP’s approach to open science has solidified and evolved over its first three years, data and metrics on progress, and CC-BY versions of assets that can be adopted and adapted by others. ASAP plans to update the Blueprint with new findings and assets on a regular basis.

This review focuses on key advances in generating new neurons through in situ neuronal reprogramming, which is tied to fundamental questions regarding adult neurogenesis, cell source, and mechanisms for neuronal reprogramming, as well as the ability of new neurons to integrate into the existing circuitry.

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.