Live-cell imaging; mitochondrial reactive oxygen species
By onThis protocol presents instructions for assessing mitochondrial souced reactive oxygen species using MitoTracker® Red CM-H2XRos dye.
Simulations predict differing phase responses to excitation vs. inhibition intheta-resonant pyramidal neurons
By onThis research highlights how cortical neurons respond differently to oscillatory inputs, impacting neuronal responses to network state shifts.
Fast Scan Cyclic Voltammetry (FSCV) in Mouse Brain Slices
By onThis protocol describes the method of fast scan cyclic voltammetry (FSCV) for the application of measuring dopamine transients in mouse brain slices. Within the protocol are sections describing the manufacture of microelectrodes, preparation of acute brain slices, fiber calibration, and measuring stimulated dopamine release.
Intracellular neuromelanin quantification
By onProtocol for intracellular neuromelanin quantification.
Primary data associated with the manuscript “Genome-wide screen reveals Rab12 GTPase as 2 a critical activator of Parkinson’s disease-linked LRRK2 kinase” (3/3)
By onPrimary data associated with the manuscript, "Genome-wide screen reveals Rab12 GTPase as 2 a critical activator of Parkinson’s disease-linked LRRK2 kinase."
Synapsin E-domain is essential for α-synuclein function
By onSynucleins and synapsins are thought to cooperate to regulate synaptic vesicle recycling, but the mechanism is not known. Here we identify the synapsin E-domain as an essential binding partner of α-syn, enabling the function of α-syn at the synapse.
LRRK2 regulates the activation of the unfolded protein response and antigen presentation in macrophages during inflammation
By onAbsence of PINK1 leads to MitAP over-activation engaging autoimmune mechanisms. This pathway is induced by TLR4, cGAS-STING, and UPR activation in response to inflammatory signals. LRRK2 and STING regulate transition from innate to adaptive immunity
Crystal structure ATG9 HDIR in complex with the ATG13:ATG101 HORMA dimer
By onCrystal structure ATG9 HDIR in complex with the ATG13:ATG101 HORMA dimer (Method: X-RAY DIFFRACTION Resolution: 2.41 Å R-Value Free: 0.251 R-Value Work: 0.204 R-Value Observed: 0.205)
Neuromelanin accumulation drives endogenous synucleinopathy in non-human primates
By onA new NHP PD model was developed by inducing neuromelanin (NM) accumulation in dopaminergic neurons, leading to synucleinopathy and neuron degeneration similar to human PD neuropathology. Lowering NM levels may offer PD therapeutic strategies.
NAP1-mCherry
By onThis protocol describes how to express and purify human NAP1 tagged C-terminally with mCherry.
AAVS1 Knock-in
By onThis protocol describes the standard procedure to knock-in constructs to the AAVS1 safe harbor locus in hPSCs.
Glucocerebrosidase is imported into mitochondria and preserves complex I integrity and energy metabolism – ASAP protocol collection
By onCollection of protocols of Deleidi Lab used in the publication: "Glucocerebrosidase is imported into mitochondria and preserves complex I integrity and energy metabolism."
Protocol for hippocampal neuronal cultures
By onThis protocol details the procedue for preparation of neuronal culturs from mice hippocampi as it was performed in Guillén-Samander et al. 2021 article "VPS13D bridges the ER to mitochondria and peroxisomes via Miro" but can also be used to prepare culturs of cortical neurons.
Genome-wide determinants of mortality and motor progression in Parkinson’s disease
By onThe 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.
Neuropathological Features of Gaucher Disease and Gaucher Disease with Parkinsonism
By onDeficient acid β-glucocerebrosidase activity due to biallelic mutations in GBA1 results in Gaucher disease (GD). Patients with this lysosomal storage disorder exhibit a wide range of associated manifestations, spanning from virtually asymptomatic adults to infants with severe neurodegeneration. While type 1 GD (GD1) is considered non-neuronopathic, a small subset of patients develop parkinsonian features. Variants in GBA1 are also an important risk factor for several common Lewy body disorders (LBDs). Neuropathological examinations of patients with GD, including those who developed LBDs, are rare. GD primarily affects macrophages, and perivascular infiltration of Gaucher macrophages is the most common neuropathologic finding. However, the frequency of these clusters and the affected anatomical region varies. GD affects astrocytes, and, in neuronopathic GD, neurons in cerebral cortical layers 3 and 5, layer 4b of the calcarine cortex, and hippocampal regions CA2–4. In addition, several reports describe selective degeneration of the cerebellar dentate nucleus in chronic neuronopathic GD. GD1 is characterized by astrogliosis without prominent neuronal loss. In GD-LBD, widespread Lewy body pathology is seen, often involving hippocampal regions CA2–4. Additional neuropathological examinations in GD are sorely needed to clarify disease-specific patterns and elucidate causative mechanisms relevant to GD, and potentially to more common neurodegenerative diseases.
Biochemical detection of aggregated Tau
By onThis protocol is associated with the following preprint, published on February 19th 2022: The AAA+ chaperone VCP disaggregates Tau fibrils and generates aggregate seeds Itika Saha, Patricia Yuste-Checa, Miguel Da Silva Padilha, Qiang Guo, Roman Körner, Hauke Holthusen, Victoria A. Trinkaus, Irina Dudanova, Rubén Fernández-Busnadiego, Wolfgang Baumeister, David W. Sanders, Saurabh Gautam, Marc I. Diamond, F. Ulrich Hartl, Mark S. Hipp bioRxiv 2022.02.18.481043; doi: https://doi.org/10.1101/2022.02.18.481043