Several life threatening inherited neurodegenerative diseases called lysosomal storage disorders have been reversed by scientists at the Icahn School of Medicine at Mount Sinai.
The proper function of the mitochondria and lysosomes was restored by the team led by Mount Sinai's Yiannis Ioannou. The energy within cells is produced by the Mitochondria. The findings were reported in a journal.
Dr. Ioannou is a professor at the Icahn School of Medicine.
Genetic defects that prevent the cell's lysosomes from breaking down and recycling fats, sugars, and proteins lead to their accumulation in organs. Further damage to these organs can be caused by this.
The study sought to uncover what it wanted to uncover.
Researchers have been searching for drugs that could affect the lysosomes. This is a new way of looking at these diseases. The cell's proper balance was promoted by increasing TRAP 1 activity. The first-in-class molecule reduces storage in lysosomal storage diseases.
There are multiple disorders that affect the central nervous system that could be treated with mitochondrial TRAP1, according to the data. The "crosstalk" between mitochondria and lysosomes was found to be essential to restoring the internal cellular balance. When activated, TRAP1, leads to restoration of normal lysosomal function in lysosomal storage diseases. This crosstalk circumvents the genetic defect that causes each lysosomal disease.
The team showed that increasing the activity of TRAP1 in cells from people with C1 could correct the disorder and restore normal cholesterol levels. Increasing TRAP1 activity in patient cells from other LSDs corrected their lipid storage. The body's ability to metabolize fat is affected by a rare disorder.
The test was developed by Dr. Ioannou and his colleagues. The test was used by the scientists to quickly sift through thousands of compounds.
They found that compounds that were activated by TRAP1 made the mitochondria work again and helped reduce the amount of fat in the lysosomes. The researchers tested the compounds further and found that they worked best.
The findings may have implications for other neurodegenerative diseases that have the same underlying causes.
The scientists would like to understand more about how the compounds can reverse the characteristics of the lysosomal storage diseases. They plan to continue refining these compounds and looking at their effects on neurological disorders such as Alzheimer's and Parkinson's diseases.
More information: Fannie W. Chen et al, Activation of mitochondrial TRAP1 stimulates mitochondria-lysosome crosstalk and correction of lysosomal dysfunction, iScience (2022). DOI: 10.1016/j.isci.2022.104941 Journal information: iScience
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