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- Table of Contents
Facts about Leucine-rich repeat serine/threonine-protein kinase 2.
Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose 6 phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent method. Regulates neuronal process morphology in the whole central nervous system (CNS).
Mouse | |
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Gene Name: | Lrrk2 |
Uniprot: | Q5S006 |
Entrez: | 66725 |
Belongs to: |
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protein kinase superfamily |
augmented in rheumatoid arthritis 17; AURA17; Dardarin; DKFZp434H2111; EC 2.7.11.1; FLJ45829; leucine-rich repeat kinase 2; leucine-rich repeat serine/threonine-protein kinase 2; LRRK2; PARK8; PARK8DARDARIN; Parkinson disease (autosomal dominant) 8; RIPK7; ROCO2
Mass (kDA):
284.732 kDA
Mouse | |
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Location: | 15|15 E3 |
Sequence: | 15; |
Expressed in the brain (at protein level). Detected throughout the adult brain. Expressed in deep cerebral cortex layers, superficial cingulate cortex layers, the piriform cortex, hippocampal formation, caudate putamen, substantia nigra, the basolateral and basomedial anterior amygdala nuclei, reticular thalamic nucleus and also in the cerebellar granular cell layer. Highly expressed in the striatum, cortex and olfactory tubercle. Little or no expression in the substantia nigra, where dopaminergic neurons preferentially degenerate in Parkinson disease. Expression is particularly high in brain dopaminoceptive areas. High and strikingly specific expression in striatum and parts of cortex and no signals in dopamine neurons.
Boster Bio has made it simple to identify antibodies for the LRRK2 kinase. To ensure the highest specificity and affinity, each antibody is tested on a variety of platforms. This includes positive and negative samples. Boster acknowledges the product's creators as the first reviewers and thanks scientists from all over the world who have conducted tests on the antibody. Their scientific literature also credits the antibody. It is used to determine the targets of your study and to measure the amount of them in the body.
The Anti-LRRK2 Marker found in the Boster Bio catalog is an ELISA kit that is designed to detect the presence of phosphorylated LRRK2. The topology of the kinase domain of LRRK2 is pictured above. These are phosphorylation locations and mutations that separate from diseases. In blue and red, risk variants and pathogenic mutants are noted. The most well-studied sites are bold.
LRRK2 is expressed by immune cells and enhanced by IFN-g. We utilized cDNA from the Clontech panel to conduct RT-PCR on American Type Culture Collection cell lines. The amplicons with unique sequences that correspond with GAPDH or LRRK2 were later detected in acrylamide gels. We normalized LRRK2 mRNA to that of THP-1 cells, which were transformed into macrophages and treated IFN-a and IFN-g. Finally, we treated the cells with the peptidoglycan (10mg/ml).
Anti-LRRK2 was first characterized in monocytes from humans. LRRK2 is found in many tissues, including the brain and kidney. It is present in the cytoplasm as well as immune cells. It can also be found in infected cells. The mRNA level of LRRK2 in boster bio is the lowest among the cultured cells from these animals.
The phosphorylation site for LRRK2 is heterologous. Some of its functions are affected by homologous phosphorylation, such as LRRK2-related GTPase activity. The role of LRRK2 in the body remains unknown, however the marker is associated with Parkinson's disease. This antibody was derived from cDNA of the wild type of the LRRK2 gene.
The progression of disease is directly related to LRRK2 phosphorylation. Certain clinical manifestations are linked to certain levels of LRRK2 protein phosphorylation, as per studies. These findings do not align with those obtained in animal models and human brain cells. This is the reason why further research is required to better discover the mechanisms that govern LRRK2 phosphorylation. It is crucial to keep in mind that the protein can be phosphorylated in a variety of locations.
Using the LRRK2 marker in biofluids enables researchers to measure the function of the kinase various patients. In addition to blood samples, LRRK2 inhibition can also be measured in urine and CSF. Researchers can monitor the effectiveness of LRRK2-targeting therapies using an orthogonal LRRK2 marker in a non-invasive method using orthogonal LRRK2 markers.
To determine LRRK2 researchers employ an exact method known as SISCAPA. This method reduces the complexity of the sample and allows for the identification of peptide species that are distinct from each other. Samples that contain the protein of interest are digested by a protease before the peptides are isolated using anti-peptide antibodies. The resulting eluent consists of peptides from the entire protein and proteases. The SISCAPA assay can serve as a marker of the entire LRRK2 or kinase activity.
LRRK2 autophosphorylation is a useful test of LRRK2 activation. The degree of auto-phosphorylation varies on the cell type and tissue it comes from. In 2016, Rab GTPases were identified as endogenous substrates for LRRK2. The switch II domain is a well-known residue in LRRK2 that is phosphorylated and robustly in both cellular and in vivo conditions.
LRRK2 genetic testing has been linked to a-synuclein, GCase activity, and other proteins. There is some uncertainty about whether these elements are associated with the LRRK2 marker. LRRK2 is elevated in the levels of proteins in Parkinson's disease. Furthermore, phosphorylation is elevated. Interestingly, the LRRK2 marker is a helpful diagnostic tool in this type of disease.
The LRRK2 gene is involved in disease progression and is a biomarker which can be used to design new treatments for Parkinson's. A range of 2 to 5 percent of all cases in North American Caucasians who suffer from Parkinson's disease are linked to the LRRK2 gene. LRRK2 hyperactivation is linked to pathogenic LRRK2 mutations. The LRRK2 marker may aid in the identification and treatment of the most effective therapies.
In recent studies, Denali Therapeutics reported positive results from the first phase of clinical trials of their LRRK2 inhibitor DNL151. The LRRK2 inhibitors were found to reduce pS935-LRRK2 and pT73-Rab10 levels in brain and lung tissue, respectively. Macaques in preclinical studies also revealed a decrease in pT73Rab10 levels in lung and brain tissue.
LRRK2 inhibition can be measured in blood, urine, and CSF. Drugs that block LRRK2 have higher plasma concentrations than those that don't. Clinical trials are currently in progress to study these drug-targeting molecules. These studies are likely to provide further insight into the efficacy of the drugs and their safety. Pharmacokinetics and pharmacodynamics of LRRK2 marker are important for clinical trials.
Recent research has demonstrated that GNE9605 binds LRRK2 extremely precisely and is highly selective in screening for kinase in kinase panel screens. It is extremely bioavailable and has an unbound brain to plasma AUC ratio of 0.5 to 1.0. It is not a CYP inhibitor or inducer drug and was well tolerated by humans.
The brain activity of numerous target proteins is affected by drug-induced pharmacokinetics and drug-drug interactions (LRRK2) of the LRRK2 Protein. LRRK2 has been proven among other things to increase the levels of phosphorylation for Rab8A, of Rab10, and of Rab8A. Studies have also revealed that neurons made from genetically modified mice have elevated levels of LRRK2 protein.
The G2019S mutation may be associated with specific BMP species in urine. This could indicate endolysosomal dysfunction. Researchers looked at BMP levels in LRRK2 carriers and non-carriers to determine whether these markers were associated with lower cognitive performance. The research also found that higher levels of urinary BMP are associated with lower cognitive performance. However, it is not clear if these markers are biomarkers for disease progression.
The most promising candidate biomarkers of LRRK2 activity are phosphoinositide isoforms. These are phosphoinositoside-based metabolites that are derived from the metabolism of phosphoinositol by LRRK2. Kinases that inhibit these can be stopped by increasing the amount of phosphoinositol.
LRRK2 hyperactivation can be connected to Parkinson's disease or pathogenic mutations. It is possible to identify the most effective therapies targeting LRRK2 through reliable measures of LRRK2 inhibition. These markers are likely to be crucial in drug development. This study shows how the LRRK2 marker could be used in clinical trials to assess the efficacy of a drug.
It has taken a lot of effort to determine the role of LRRK2 in PD. It has been linked to motor neuron disease, progressive supranuclear paralysis, multiple system atrophy, and multiple system atrophy. It also plays a role in the regulation of the morphology of the neurite process. The LRRK2 marker is not widely used, but its presence in the general population, is useful for diagnosing and conducting research.
The LRRK2 gene is present in many tissues. The LRRK2 gene is expressed on the level of the LRRK2 protein in cells like the brain. A recent study showed that the LRRK2 gene expression in the brain correlates with the amount of protein in blood, urine, and CSF. In turn, LRRK2 inhibitory activity can be used to assess the efficacy of treatments.
LRRK2 is a protein found in membrane microdomains, microvilli/filopodia, and cytoplasmic puncta. LRRK2 is linked with the lysosomal pathway which promotes autophagy. Mutations in LRRK2 have been linked to autophagic stress. For instance, the R1441C mutation can cause abnormal autophagic vacuoles. These abnormal AVs affect neighboring untransfected cells.
Biomarkers that target LRRK2 may be more appropriate than biomarkers which measure bioavailability. There are no biomarkers that could be used to identify LRRK2 because the LRRK2 gene has not been fully comprehended. But, the rapid developments in this field make the LRRK2 gene a great candidate for enrichment strategies using biomarkers. What are the advantages and disadvantages of a biomarker with LRRK2 as a base?
LRRK2 has been linked to PD pathogenesis. LRRK2 is an enzyme that plays an important role in the immune system. It is also present in neural cells and antigen-presenting cells lines. LPS is a bacterial protein which triggers immune responses stimulates it in mice. In vitro studies have demonstrated that LRRK2 hinders the activity of GSK-3b which is a transcription factor implicated in the activation of pro-inflammatory T cells.
PMID: 15541309 by Zimprich A., et al. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology.
PMID: 16532471 by Galter D., et al. LRRK2 expression linked to dopamine-innervated areas.