The study links ISN1 gene variations with increased risk of Parkinson’s disease

A new study published in Cell reports reveals a discovery discovery that connects genetic variants to the gene Itsn1 In a significantly increased risk of Parkinson’s disease, a neurodegenerative condition affecting almost 2% of adults over 65 years. This project, led by an international team of researchers at Baylor College of Medicine, Astrazeneca and the Institute of Neurological Research Jan and Dan Duncan at the Texas Children’s Hospital, could pave the way for new therapies aimed at deceleration or prevention of Parkinson.

Parkinson’s disease, the second most common neurodegenerative disorder, has no treatment yet. To deal with this unfulfilled need, we analyzed genetic data from about 500,000 participants in the UK Biobank and discovered that people who rarely carry rare Itsn1Variations that damage the normal function of the gene facing up to ten times higher risk of developing Parkinson’s disease. ”

Dr. Ryan S. Dhindsa, co-by-in-law, Assistant Professor of Pathology and Immunology at Baylor College of Medicine and the main researcher at Jan and Dan Duncan Institute of Neurological Research

These findings were then validated in three independent groups that include more than 8,000 cases and 400,000 checks. Is important, Itsn1 Carriers tend to the previous age of developing the disease.

“What makes this discovery so important is the excellent size of the effect Itsn1 In increasing the risk of Parkinson, especially compared to variations in other well -established genes such as Lrrk2 and Gba1“Dhindsa said.

“We focus on rare genetic mutations because they often give great effects on the risk of illness that reveal critical disease mechanisms. These genetic discoveries not only deepen our understanding of Parkinson’s biology but also reveal new goals for therapeutic.”

Itsn1 It plays an important role in the way neurons send messages to each other – a process called synaptic transmission – making it particularly relevant to Parkinson’s disease, a condition in which the breakdown of nerve signals leads to the typical symptoms of reduced walking and balance and balance. “We have also shown in fruit flies that reduce Itsn1 Levels worsen characteristics that look like Parkinson, including the ability to rise. We are planning to expand these research into stem cells and mice models, “Dhindsa said.

Interestingly, previous studies have recently engaged in similar Itsn1 Mutations in autism spectrum disorder (ASD). Other emerging data have also suggested a correlation between ASD’s disease and Parkinson, indicating that people with ASD are three times more likely to develop parkinsonism. “Our findings support future studies to better understand the connections between these two conditions and the mechanisms involved,” Dhindsa said.

This study underlines Itsn1 As a promising therapeutic goal and emphasizes the value of the large scale of genetic sequence in identifying rare mutations that contribute to complex neurological disorders.

Other contributors to this project include Thomas P. Spargo, Chloe F. Sands, Isabella R. Juan, Jonathan Mitchell, Vida Ravanmehr, Jessica C. Butts, Ruth B. De-Paula, Youngdoo Kim, Fengyuan Hu, Quanli Wang, Dimitrios Vitsios, Manik, Lawrenc Guillermo del Angel, Daniel G. Calame, Hiba Saade, Laurie Robak, Ben Hollis, Vishnu A Cuddapah, Huda Y. Zoghbi, Joshua M. Shulman, Slavé Petrovski, Imael Al-Ramahi and Ioanna Tachmazidou. The authors are linked to one or more of the following institutions: Baylor College of Medicine, Astrazeneca, the Institute of Neurological Research Jan and Dan Duncan at Texas Children’s Hospital, Rice University and the University of Melbourne.