Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures
By onRecent findings identified PD-associated autoimmune features. Using RNA sequencing, the authors found a broad gene expression profile in memory T cells and a specific PD-associated gene signature.
Genetic variations in GBA1 and LRRK2 genes: Biochemical and clinical consequences in Parkinson disease
By onVariants in the GBA1 and LRRK2 genes are the most common genetic risk factors associated with Parkinson disease (PD). Both genes are associated with lysosomal and autophagic pathways, with the GBA1 gene encoding for the lysosomal enzyme, glucocerebrosidase (GCase) and the LRRK2 gene encoding for the leucine-rich repeat kinase 2 enzyme. GBA1-associated PD is characterized by earlier age at onset and more severe non-motor symptoms compared to sporadic PD. Mutations in the GBA1 gene can be stratified into severe, mild and risk variants depending on the clinical presentation of disease. Both a loss- and gain- of function hypothesis has been proposed for GBA1 variants and the functional consequences associated with each variant is often linked to mutation severity. On the other hand, LRRK2-associated PD is similar to sporadic PD, but with a more benign disease course. Mutations in the LRRK2 gene occur in several structural domains and affect phosphorylation of GTPases. Biochemical studies suggest a possible convergence of GBA1 and LRRK2 pathways, with double mutant carriers showing a milder phenotype compared to GBA1-associated PD. This review compares GBA1 and LRRK2-associated PD, and highlights possible genotype-phenotype associations for GBA1 and LRRK2 separately, based on biochemical consequences of single variants.
Free-floating Mouse Brain Immunohistochemistry
By onThis protocol enables immunohistochemical staining of murine tissue with superior penetration of the tissue by the reagents due to the free-floating approach.
Expansion of mouse embryonic fibroblasts (MEFs) for hPSC cultures
By onThis protocol describes the expansion of mouse embryonic fibroblasts (MEFs) as feeder cells for human pluripotent stem cell (hPSC) culture.
AAVS1-SA-neo-CAGGS-PE2-2A-GFP
By onIt can be used to generate knock-in cell line faciliating prime editing.
Subcellular proteomics of dopamine neurons in the mouse brain
By onUnderstanding the proteome of dopamine neuron is difficult due to the complex cytoarchitecture of the neurons. The authors were able to map the somatodendritic and axonal proteomes of midbrain dopaminergic neurons.
Cell culture, transfection, immunocytochemistry, and imaging
By onThis protocol is to help with the maintenance, transfection, immunocytochemistry, and imaging of adherent mammalian cells
Macros and pipelines for analysis of image analysis
By onImageJ macros and pipelines for analysis of pUb puncta, Keima Ratio, p62nuclei and Parkin recruitment to mitochondria.
Basal ganglia neurons in healthy and parkinsonian primates generate recurring sequences of spikes
By onBasal ganglia neurons fire in recognizable, repeating sequences of interspike intervals (ISIs), the incidence of which is influenced by the induction of Parkinsonism.
Rodent models based on endolysosomal genes involved in PArkinson’s disease
By onGenes linked to endolysosomal function are connected to Parkinson's disease, suggesting a role in its development. Rodent models targeting these genes like LRRK2 and GBA1 show parkinsonian features, aiding in understanding and treating the disease.
Genetic and pharmacological reduction of CDK14 mitigates synucleinopathy
By onDecreasing alpha-synuclein levels is a potential therapeutic approach for synucleinopathies. The authors identified CDK14 regulates alpha-synuclein and show reduction of CDK14 reduces alpha-synuclein and PD-like characteristics.
Purification and analysis of SKP1-FBXO7 complexes
By onProtocol for the biochemical purification and analysis of SKP1-FBXO7 complexes.
Preparation of LRRK2 RCKW cryo-EM grids
By onThis is Leschziner's Lab updated protocol for making cryo-EM grids for LRRK2 RCKW. This protocol, when using lower protein concentration, results in better monomer and dimer formation than the old protocol.
Fixation of HeLa-M cells expressing Halo and SNAP fusion proteins conjugated to ligands
By onProtocol describing fixation of HeLa-M cells expressing Halo and SNAP fusion proteins conjugated to ligands.
Soluble and insoluble A-SYN fractionation
By onSoluble/insoluble alpha-synuclein fractionation is a technique used to separate different forms of the alpha-synuclein protein based on their solubility properties.
