Sex-Specific Microglial Responses to Glucocerebrosidase Inhibition: Relevance to GBA1-Linked Parkinson’s Disease
By onMicroglia are heterogeneous cells characterized by distinct populations, each contributing to specific biological processes in the nervous system, including neuroprotection. To elucidate the impact of sex-specific microglia heterogenicity to the susceptibility of neuronal stress, we video-recorded with time-lapse microscopy the changes in shape and motility occurring in primary cells derived from mice of both sexes in response to pro-inflammatory or neurotoxic stimulations. With this morpho-functional analysis, we documented distinct microglia subpopulations eliciting sex-specific responses to stimulation: male microglia tended to have a more pro-inflammatory phenotype, while female microglia showed increased sensitivity to conduritol-B-epoxide (CBE), a small molecule inhibitor of glucocerebrosidase, the enzyme encoded by the GBA1 gene, mutations of which are the major risk factor for Parkinson’s Disease (PD). Interestingly, glucocerebrosidase inhibition particularly impaired the ability of female microglia to enhance the Nrf2-dependent detoxification pathway in neurons, attenuating the sex differences observed in this neuroprotective function. This finding is consistent with the clinical impact of GBA1 mutations, in which the 1.5–2-fold reduced risk of developing idiopathic PD observed in female individuals is lost in the GBA1 carrier population, thus suggesting a sex-specific role for microglia in the etiopathogenesis of PD-GBA1
Software for analyzing the expression of TEs at locus-specific resolution
By onWe enable the locus-specific analysis of transposable elements, with curated GTF files to improve detection of yound transposable elements, such as HERVs and young L1s. Parts of this software will be used for single-cell TE anlaysis protocols, which are under development
Immunofluorescence of RAB5 and FLAG-EEA1 puncta after Dynamin-1 and -2 inhibition with Dyngo4a
By onSelective purification of early endosomes can be achieved through affinity capture of the early endosome-associated protein EEA1 (termed Endo-IP) (Park et al. in submission). These purified endosomes can be used for proteomic and lipidomic studies to obtain snapshots of early endosomes. Here we present an immunofluorescence protocol to assess the extent of colocalization between FLAG-EEA1 and RAB5 with and without the Dynamin-1 and -2 (DNM1/2) inhibitor Dyngo4a.
H9 ES AAVS1-NGN2 FAM134B-/-
By onCell Line: ES cells for making iNeurons lacking the ER-phagy receptor FAM134B.
Local diffusion in the extracellular space of the brain
By onThe authors highlight emerging technological advances to respectively interrogate and model diffusion through the ECS, and point out how these may contribute in resolving the remaining enigmas of the ECS.
Novel green fluorescent polyamines to analyze ATP13A2 and ATP13A3 activity in the mammalian polyamine transport system
By onBiochemical evidence presented here shows that fluorescently labeled polyamines are genuine substrates of ATP13A2.
Vibrational Stabilization of Complex Network Systems
By onMany natural and man-made network systems need to maintain certain patterns, such as working at equilibria or limit cycles, to function properly. The authors provide some numerical results that demonstrate the validity of the theoretical findings.
Manual Tracking/image_prep.ijm
By onA script to register 2-channel timelapse images using HyperStackReg, using only 1 of the channels to compute transformation. The script also enhances contrast and prepares the image for manual tracking.
Manual Tracking/measure_ECM.ijm
By onA script to generate circular ROIs in each frame of a timelapse, using a previously generated track as reference. Used to measure fluorescence intensity (i.e., extracellular matrix content) along a microglia track. .
Manual Tracking/tracking.ijm
By onA script to store in ImageJ’s ROImanager the tracks generated using Manual Tracking plugin, for later use (drawing tracks, frame-by-frame analysis). To be used as a continuation of 1_image_prep.ijm.
Preparation of unilamellar liposomes
By onA protocol for preparing liposomes that can be used to monitor binding of proteins to vesicles of various membrane curvatures.
A computational pipeline to quantify primary cilia in mouse embryonic fibroblasts with CellProfiler
By onThis protocol works with .czi format images which are acquired using a Zeiss laser scanning confocal microscope and are maximum intensity projected.
Genetic meta-analysis of levodopa induced dyskinesia in Parkinson’s disease
By onBased on a functional annotation analysis on chromosome 1, the authors determined that changes in DNAJB4 gene expression is an additional potential cause of increased susceptibility to LiD.
Detecting rhythmic spiking through the power spectra of point process model residuals
By onThe work highlighted in this manuscript improves the ability to characterize oscillatory activity and detect pathological changes at the level of individual neurons.
Standard Operating Procedure (SOP) for Combined ICA and Systemic Administration of MPTP: The Overlesioned (Bilateral Asymmetric) Non-human Primate Model
By onThis standard operating procedure (SOP) describes safe methods for the use of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in non-human primates (adult macaque monkeys).
Mitochondrial degradation: Mitophagy and beyond
By onMitochondria are vital for cellular function. Degradation pathways like mitophagy regulate their quality and activity. Various mechanisms, such as mitophagy and mitochondrial extrusion, ensure cellular homeostasis by removing unwanted mitochondria.
Parkinson’s genes orchestrate pyroptosis through selective trafficking of mtDNA to leaky lysosomes
By onThese data place mitochondria-to-lysosome transport as a driver of pyroptosis and link multiple PD proteins along a common inflammatory pathway.
