Publications by authors named "Anton Saalfrank"
ALPK1 mutants causing ROSAH syndrome or Spiradenoma are activated by human nucleotide sugars.
Proc Natl Acad Sci U S A
December 2023
Article Synopsis
- The protein kinase ALPK1, which is normally activated by the bacterial sugar ADP-heptose, phosphorylates TIFA to initiate an immune response against infections.
- Mutations in ALPK1, specifically ALPK1[T237M], ALPK1[Y254C], and ALPK1[V1092A], are linked to serious human diseases like ROSAH syndrome and certain types of skin tumors called spiradenoma and spiradenocarcinoma.
- Unlike the normal ALPK1, these mutations allow activation of the signaling pathway even without ADP-heptose, responding instead to other sugars found in human cells, indicating a loss of specificity that contributes to the diseases.
Leucine-rich repeat kinase 2 (LRRK2) is one of the most promising targets for Parkinson's disease. LRRK2-targeting strategies have primarily focused on type 1 kinase inhibitors, which, however, have limitations as the inhibited protein can interfere with natural mechanisms, which could lead to undesirable side effects. Herein, we report the development of LRRK2 proteolysis targeting chimeras (PROTACs), culminating in the discovery of degrader XL01126, as an alternative LRRK2-targeting strategy.
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