Publications by authors named "L Caberlotto"
The G2019S variant of LRRK2, which causes an increase in kinase activity, is associated with the occurrence of Parkinson's disease (PD). Potent, mutation-selective, and brain penetrant inhibitors of LRRK2 can suppress the biological effects specific to G2019S-LRRK2 that cause pathogenicity. We report the discovery of a series of cyanoindane and cyanotetralin kinase inhibitors culminating in compound 34 that demonstrated selective inhibition of phosphorylation of LRRK2 in the mouse brain.
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- The metabotropic glutamate receptor 1 (mGlu) is crucial for synaptic transmission and neuronal plasticity, but its protein interactions in specific brain regions, like the cerebellum, are not fully understood.
- Researchers used a proteomic approach to identify associated proteins, discovering well-known complexes and a novel interactor called KCTD12.
- Further experiments showed that KCTD12 and mGlu are located close to each other in Purkinje cell spines, suggesting a potential but indirect interaction, without being mediated by GABA receptors.
The humoral response to SARS-CoV-2 vaccination has shown to be temporary, although may be more prolonged in vaccinated individuals with a history of natural infection. We aimed to study the residual humoral response and the correlation between anti-Receptor Binding Domain (RBD) IgG levels and antibody neutralizing capacity in a population of health care workers (HCWs) after 9 months from COVID-19 vaccination. In this cross-sectional study, plasma samples were screened for anti-RBD IgG using a quantitative method.
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- A significant portion of the global population suffers from metabolic diseases (MD), with projections indicating a potential doubling of cases in the coming decades, leading to additional health challenges like NAFLD and cardiomyopathy.
- The investigation of genetic factors contributing to MD typically uses biological network analysis but faces issues like data bias and complexity in methodology.
- The proposed approach introduces a straightforward, parameter-free method that considers the effects of database dependence and network topology, helping to identify key genes linked to MD and suggesting new candidates for further research.
Pathogenic variants in the leucine-rich repeat kinase 2 (LRRK2) gene have been identified that increase the risk for developing Parkinson's disease in a dominantly inherited fashion. These pathogenic variants, of which G2019S is the most common, cause abnormally high kinase activity, and compounds that inhibit this activity are being pursued as potentially disease-modifying therapeutics. Because LRRK2 regulates important cellular processes, developing inhibitors that can selectively target the pathogenic variant while sparing normal LRRK2 activity could offer potential advantages in heterozygous carriers.
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