Projects & Grants




Molekulární, buněčný a klinický přístup ke zdravému stárnutí
Project IdCZ.02.1.01/0.0/0.0/16_019/0000868
Main solverprof. MUDr. Roman Hájek, CSc.
Period9/2018 - 6/2023
ProviderOperační program Výzkum, vývoj a vzdělávání (OP VVV)
Statesolved
AnotationAssociation of ribosomal gene expression disbalance with cell senescence and production of amyloidogenic immunoglobulin in AL amyloidosis: Based on our preliminary results (described in Research activities leading to achievement of the objective section) we hypothesize the involvement of ribosomal machinery in the pathogenesis of amyloid deposits formation. So far, impact of the ribosome biogenesis and translation changes on the pathogenic development of AL amyloidosis has not been studied. However, we suppose that the impaired ribosome function may have an important role also in the synthesis of aberrant amyloid protein and AL amyloidosis. The ribosome filter hypothesis postulates that ribosomes are not simply translation machines but also serve as regulatory elements that differentially affect or filter the translation of particular mRNAs (PMID:17890902). Besides, there is a concept of ?specialized ribosomes?, in which tissue-specific variations in ribosomal structure or function confer regulatory specificity in translation (PMID:22617470).. Ribosome biogenesis and its enzymatic activity represent the essential cellular processes and their impairments are associated with defects in distinct types of cellular responses, including translational control, apoptosis, cell senescence and others (PMID:26068591, 25732822, 19779612).Apart from mutations in ribosomal machinery related genes, production of amyloidogenic protein itself affects post-transcriptional disbalance in general. This disbalance is mainly associated with translational initiation, elongation and protein folding. This hypothesis is potentially relevant in the investigation of other age-related ?amyloid-?? like diseases pathobiology.