Publications by authors named "P M van Endert"

Patients with pathogenic variants in the gene suffer from severe and recurrent rhabdomyolysis episodes precipitated by fasting. Autophagy functioning was analyzed , in primary skeletal myoblasts from TANGO2 patients, in basal and fasting conditions, and mutations were associated with reduced LC3-II levels upon starvation. In zebrafish larvae, inhibition induced locomotor defects which were exacerbated by exposure to atorvastatin, a compound known to cause rhabdomyolysis.

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Type 1 diabetes results from the destruction of pancreatic beta cells by autoreactive T cells. As an autoantigen with extremely high expression in beta cells, insulin triggers and sustains the autoimmune CD4 and CD8 T cell responses and islet inflammation. We have previously shown that deficiency for insulin-degrading enzyme (IDE), a ubiquitous cytosolic protease with very high affinity for insulin, induces endoplasmic reticulum (ER) stress and proliferation in islet cells and protects non-obese diabetic mice (NOD) from diabetes.

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Article Synopsis
  • IRAP is an enzyme found in various immune cells, and it helps regulate the body's immune response; its genetic variants are linked to survival rates in septic shock patients.
  • In a study modeling systemic inflammation from gram-negative sepsis using LPS, immune responses were compared between IRAP knockout and wildtype mice.
  • Results showed that IRAP deficiency led to increased activation and pro-inflammatory response in dendritic cells and macrophages, highlighting the enzyme's role in inflammation, which varies by time and sex.
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Article Synopsis
  • The human immune system continues to develop for several years after birth, affecting how young children respond to infections, such as SARS-CoV-2.
  • Researchers studied T cell responses in children and adults before, during, and after SARS-CoV-2 infection, revealing that younger children (under 5) had a weaker CD4 T cell response compared to older children and adults with mild disease.
  • Following infection, preschool-age children produced similar neutralizing antibodies to adults but had different T cell characteristics and fewer memory B cells, indicating a gradual maturation of their adaptive immune responses.
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Insulin-regulated aminopeptidase (IRAP) is an enzyme with important biological functions and the target of drug-discovery efforts. We combined in silico screening with a medicinal chemistry optimization campaign to discover a nanomolar inhibitor of IRAP based on a pyrazolylpyrimidine scaffold. This compound displays an excellent selectivity profile versus homologous aminopeptidases, and kinetic analysis suggests it utilizes an uncompetitive mechanism of action when inhibiting the cleavage of a typical dipeptidic substrate.

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