2024-01-18 15:30:28
1% of the European population carries this variant, located in a mitochondrial microprotein. The discovery opens the way to the development of new treatments. The discovery of a new variant that protects against Parkinson’s opens a new avenue for the development of treatments.
Researchers at the Leonard Davis School of Gerontology at the University of Southern California have found a new genetic mutation that reduces the chance of developing Parkinson’s disease by half. Its discovery opens a new avenue to explore the development of potential new antiparkinsonian treatments.
According to the article published in the latest issue of Molecular Psychiatry, this variant is located in the mitochondrial microprotein SHLP2. About 1% of the European population is a carrier of this mutation.
The discovery of SHLP2 dates back to 2016 and is signed by researcher Pinchas Cohen, from Leonard Davis. This mitochondrial microprotein has been associated with a protective effect against aging-related diseases, including cancer.
It is also known that the levels of this microprotein undergo alterations during the course of Parkinson’s disease: they increase when the body tries to counteract the pathology, but often fail to generate additional production as the disease progresses.
In a statement from the University of Southern California, Cohen explains that while most studies on the genetics of Parkinson’s focus on genes encoding known proteins in the cell nucleus, their finding reveals the interest in exploring microproteins derived from mitochondria. in the search for strategies aimed at the prevention and treatment of diseases associated with aging.
‘BIG DATA’
For this research, the researchers used the big data to identify new variants implicated in the disease, thanks to information from the Health and Retirement Study, the Cardiovascular Health Study and the Framingham Heart Study.
They saw that this newly discovered variant results in a change in the amino acid sequence and protein structure of SHLP2. The mutation (a single nucleotide polymorphism) is essentially a gain-of-function variant, which is associated with increased expression of SHLP2 which provides greater protection against mitochondrial dysfunction and also makes the microprotein more stable.
The team used mass spectrometry techniques to identify the presence of the small peptide in neurons and found that SHLP2 specifically binds to an enzyme in mitochondria called the mitochondrial complex. This enzyme is essential for life and decreases in its function have been linked to Parkinson’s disease, strokes and heart attacks.
The greater stability of the SHLP2 variant means that the microprotein binds to the mitochondrial complex more stably, preventing the decrease in enzyme activity and therefore reducing mitochondrial dysfunction. According to this work, the benefits of the mutant form of SHLP2 were observed both in experiments in vitroin human tissue samples, such as in mouse models of Parkinson’s disease.
For fellow author Su-Jeong Kim, “these findings can guide the development of therapies and provide a roadmap to understand other mutations found in mitochondrial microproteins.” Peter Inigo
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