Related Experiment Video

Updated: May 14, 2026

Detection of Nuclear Blebbing and DNA Leakage in Mammalian Cells by Immunofluorescence
06:23

Detection of Nuclear Blebbing and DNA Leakage in Mammalian Cells by Immunofluorescence

Published on: January 17, 2025

Targeting protein prenylation in progeria

Stephen G Young1, Shao H Yang, Brandon S J Davies

  • 1Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. sgyoung@mednet

Science Translational Medicine
|February 8, 2013
PubMed

Insights

A clinical trial investigated lonafarnib, a protein farnesyltransferase inhibitor, for Hutchinson-Gilford progeria syndrome (HGPS). The study discusses the disease mutation, treatment rationale, limitations, and future therapeutic strategies for HGPS.

Area of Science:

  • * Molecular biology and genetics
  • * Clinical pharmacology and drug development

Background:

  • * Hutchinson-Gilford progeria syndrome (HGPS) is a rare, fatal genetic disorder characterized by premature aging.
  • * The disease is caused by a specific point mutation in the LMNA gene, leading to the production of progerin, an abnormal protein.
  • * Progerin accumulation disrupts nuclear structure and cellular function, driving the pathology of HGPS.

Purpose of the Study:

  • * To evaluate the efficacy and safety of lonafarnib, a protein farnesyltransferase inhibitor, in a clinical trial for HGPS patients.
  • * To explore the underlying genetic mutation and the mechanistic rationale for targeting protein farnesyltransferase in HGPS.
  • * To identify potential limitations of lonafarnib therapy and propose novel therapeutic strategies for HGPS.

Main Methods:

  • * A clinical trial was conducted to assess the effects of lonafarnib in patients with HGPS.
  • * The study involved analyzing the genetic basis of HGPS and the biochemical pathway targeted by the drug.
  • * Discussion of potential therapeutic challenges and future research directions.

Main Results:

  • * A clinical trial of lonafarnib for HGPS was completed.
  • * The study provides insights into the mutation causing HGPS and the rationale for using protein farnesyltransferase inhibitors.
  • * Discussion includes limitations of the current approach and potential future strategies.

Conclusions:

  • * Lonafarnib represents a targeted therapeutic approach for Hutchinson-Gilford progeria syndrome.
  • * Understanding the disease's genetic underpinnings is crucial for developing effective treatments.
  • * Further research is needed to overcome therapeutic limitations and explore novel strategies for HGPS.

More Related Videos

Assays for the Degradation of Misfolded Proteins in Cells10:56

Assays for the Degradation of Misfolded Proteins in Cells

Published on: August 28, 2016

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors08:45

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors

Published on: July 17, 2020

Related Concept Videos

Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Directing Proteins to the Rough Endoplasmic Reticulum01:34

Directing Proteins to the Rough Endoplasmic Reticulum

The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...