(ESP) Translation by Marion Clark and Juan Carlos Baiges Frataxin deficiency, mitochondrial Lon and ClpP and Fe-S proteins: clarifications by Juan Carlos Baiges Note: The abstract of this article was published in English and sent to FA_babelFAmily by Juan Carlos Baiges, a Spanish pharmacist and parent of a child with FA, who then provided a layman's explanation of the abstract at the request of an Internaf member. This is a translation of his explanation, which was written in Spanish. Translator's note: Enzymes are biomolecules that catalyze (set in motion) chemical reactions. Almost all enzymes are proteins. Proteases are a type of enzymes which conduct the process of proteolysis, or begin breaking down other proteins, by breaking the bonds that form them into amino acid chains. Both Lon and ClpP are proteases. Hello Gian, Although I am not an expert in this subject, I'm sending this brief summary with the points that I think are most relevant and some comments. Greetings, Juan Carlos Original source: http:/// (ESP) In this article the authors show us that there is a relationship between frataxin deficiency and certain proteases, Lon and ClpP. These proteases are enzymes responsible for keeping the mitochondria free of abnormal proteins by breaking down the abnormal proteins. The most significant increase in Lon and ClpP occurs midway through the development of the disease. In addition, the authors observed a large decrease in the proteins involved with the Fe-S (iron-sulfur) clusters, without there being any change in the level of genetic transcription. For this reason they speculate that Lon and ClpP are possibly responsible for the elimination of these Fe-S proteins because the latter are considered abnormal or unnecessary. With the current knowledge, it appears (on the up side) that the increase of Lon and ClpP is beneficial for "cleaning up" the mitochondria, but it also appears (on the down side) that this increase in Lon and ClpP can hide the increase in oxidative damage. When there are more data available about how, and about which substrates (molecules on which the enzymes act) activate these proteases (the authors indicate that they've already begun these studies), then it will be possible to know what role these proteins play in the evolution of the disease, and to clarify even further the function of frataxin. Lon and ClpP are two important proteases responsible for eliminating proteins defective due to having been misfolded. The proteins have to acquire a 3-dimensional form after their synthesis in order to be active, and different enzymes and chaperones intervene in this process. It is known that the proteins Lon and ClpP are very important for the correct function of the mitochondria, and they are expressed in large numbers in the cells with large energy requirements, such as those of the heart and of the skeletal muscles. In this study the authors demonstrate that the deficiency of frataxin causes an increase, or upregulation, in the quantity of these proteins, Lon and ClpP, in the mitochondria, and this increase occurs at the middle stages of the development of the disease. This increase takes place through two different mechanisms, in Lon by regulation in the transcription, and in ClpP through either a translational or a post-translational mechanism. Even though little is yet known about it, Lon is a multifunctional protein which could have many functions; in this study, they show that in the heart Lon acts as a proteolytic enzyme, eliminating defective proteins. In this study they also show that frataxin deficiency can cause a significant loss of certain mitochondrial iron-sulfur (Fe-S) enzymes, without it being due to change in transcription. Through statistical analysis, they relate the decrease in frataxin with an increase in the proteases Lon and ClpP, and they speculate that the defects in the formation of Fe-S clusters (due to frataxin deficiency) cause the formation of mitochondrial apoenzymes (enzymes needing a cofactor to function, but lacking that cofactor and thus inactive) which are recognized as defective and are broken down by Lon and ClpP (although they don't rule out other mechanisms).

The legacy of Marie Schlau: literature to help cure Friedreich's Ataxia

If you feel like reading an unputdownable novel while collaborating with a just and solidary cause, "The Legacy of Marie Schlau" is your book! 100% of all funds raised will be dedicated to medical research to find a cure for Friedreich's Ataxia, a neurodegenerative disease that affects mostly young people, shortening their life expectancy and confining them to a wheelchair.

The life of Marie Schlau, a German Jewish girl born in 1833 hides great unsolved mysteries: accidents, disappearances, enigmas, unknown diagnoses, disturbing murders, love, tenderness, greed, lies, death ... alternatively a different story unfolds every time and takes us closer to the present. Thus, there are two parallel stories unravelling, each in a different age and place, which surprisingly converge in a revelatory chapter.

Paperback and Kindle versions for "The legacy of Marie Schlau" available for sale at Amazon now!


Research projects currently being financed by BabelFAmily

Currently, BabelFAmily is financing two promising research projects aimed at finding a cure for Friedreich's Ataxia. Whenever you make a donation to us or purchase a copy of "The legacy of Marie Schlau", this is where all funds raised will be devoted to:

1) Gene Therapy for Friedreich's Ataxia research project:

The project is the result of an initiative of Spanish people affected by this rare disease who are grouped in GENEFA in collaboration with the Spanish Federation of Ataxias and the BabelFAmily. The Friedreich’s Ataxia Research Alliance (FARA), one of the main patients’ associations in the United States now joins the endeavour.

2) Frataxin delivery research project:
The associations of patients and families Babel Family and the Asociación Granadina de la Ataxia de Friedreich (ASOGAF) channel 80,000 euros of their donations (50% from each organisation) into a new 18-month project at the Institute for Research in Biomedicine (IRB Barcelona). The project specifically aims to complete a step necessary in order to move towards a future frataxin replacement therapy for the brain, where the reduction of this protein causes the most damage in patients with Friedreich’s Ataxia.

The study is headed by Ernest Giralt, head of the Peptides and Proteins Lab, who has many years of experience and is a recognised expert in peptide chemistry and new systems of through which to delivery drugs to the brain, such as peptide shuttles—molecules that have the capacity to carry the drug across the barrier that surrounds and protects the brain. Since the lab started its relation with these patients’ associations in 2013*, it has been developing another two projects into Friedrich’s Ataxia.



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