Permanently Farnesylated Prelamin A, Progeria, and Atherosclerosis

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Autophagic degradation of farnesylated prelamin A as a therapeutic approach to lamin-linked progeria

Farnesylated prelamin A is a processing intermediate produced in the lamin A maturation pathway. Accumulation of a truncated farnesylated prelamin A form, called progerin, is a hallmark of the severe premature ageing syndrome, Hutchinson-Gilford progeria. Progerin elicits toxic effects in cells, leading to chromatin damage and cellular senescence and ultimately causes skin and endothelial defec...

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Erratum - Autophagic Degradation of Farnesylated Prelamin a as a Therapeutic Approach to Lamin-Linked Progeria

V. Cenni,1 C. Capanni,1 M. Columbaro,2 M. Ortolani,1 M.R. D’Apice,3 G. Novelli,4 M. Fini,5 S. Marmiroli,6 E. Scarano,7 N.M. Maraldi,2 S. Squarzoni,1 S. Prencipe,5 G. Lattanzi1 1National Research Council of Italy, Institute for Molecular Genetics, IGM-CNR, Unit of Bologna c/o IOR, Bologna 2Laboratory of Musculoskeletal Cell Biology, Rizzoli Orthopedic Institute, Bologna 3Department of Biopatholo...

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An accumulation of non-farnesylated prelamin A causes cardiomyopathy but not progeria.

Lamin A is formed from prelamin A by four post-translational processing steps-farnesylation, release of the last three amino acids of the protein, methylation of the farnesylcysteine and the endoproteolytic release of the C-terminal 15 amino acids (including the farnesylcysteine methyl ester). When the final processing step does not occur, a farnesylated and methylated prelamin A accumulates in...

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Different prelamin A forms accumulate in human fibroblasts: a study in experimental models and progeria

Lamin A is a component of the nuclear lamina mutated in a group of human inherited disorders known as laminopathies. Among laminopathies, progeroid syndromes and lipodystrophies feature accumulation of prelamin A, the precursor protein which, in normal cells, undergoes a multi-step processing to yield mature lamin A. It is of utmost importance to characterize the prelamin A form accumulated in ...

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Mice that express farnesylated versions of prelamin A in neurons develop achalasia.

Neurons in the brain produce lamin C but almost no lamin A, a consequence of the removal of prelamin A transcripts by miR-9, a brain-specific microRNA. We have proposed that miR-9-mediated regulation of prelamin A in the brain could explain the absence of primary neurological disease in Hutchinson-Gilford progeria syndrome, a genetic disease caused by the synthesis of an internally truncated fo...

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ژورنال

عنوان ژورنال: Circulation

سال: 2018

ISSN: 0009-7322,1524-4539

DOI: 10.1161/circulationaha.118.034480