Summary: A new research has identified genetic variants in the ITSN1 protein that drastically increase the risk of developing Parkinson’s disease. Researchers analyzed almost 500, 000 biological information and found that individuals carrying ITSN1 variations face up to a twofold higher chance of Parkinson’s.
The study also linked ITSN1 to earlier condition beginning and impaired neurological signaling, important for motion and coordination. Experiments in fruit flies showed that reducing ITSN1 levels worsens Parkinson ‘s-like symptoms, supporting its role in disease progression.
Incidentally, related mutations in ITSN1 have been associated with autism range disorder, suggesting a possible link between ASD and Parkinson’s. These results show ITSN1 as a appealing target for potential solutions.
Important Facts:
- Biological Risk Factor: ITSN1 protein variants improve Parkinson’s risk up to twofold.
- Cerebral Impact: ITSN1 plays a vital role in neural tranny, affecting movement.
- ASD Connection: Related variants in ITSN1 have been linked to autism spectrum disorder.
Origin: Baylor College of Medicine
A new research published in , Cell Reports , reveals a miracle finding linking genetic variations in the gene , ITSN1 , to a significantly elevated risk of Parkinson’s condition, a neurological condition that affects almost 2 % of people older than 65 years.  ,
This work, led by an international team of researchers at Baylor College of Medicine, AstraZeneca and the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, could pave the way for new procedures aimed at slowing or preventing Parkinson’s disease development.
” Parkinson’s disease, the second most common neurological disorder, still has no treatment.
” To address this unmet need, we analyzed genomic data from nearly 500, 000 UK Biobank participants and discovered that individuals carrying rare , ITSN1variants that affect the bacteria’s standard function face up to a twofold higher risk of developing Parkinson’s disease,” said co-corresponding author , Dr. Ryan S. Dhindsa, assistant professor of , pathology and immunology , at , Baylor College of Medicine , and main investigator at the , Jan and Dan Duncan Neurological Research Institute , at Texas Children’s Hospital.
These findings were subsequently validated across three independent cohorts comprising more than 8, 000 cases and 400, 000 controls. Importantly,  , ITSN1 , carriers trended toward earlier age of disease onset.
” What makes this discovery so significant is the exceptional magnitude of the effect of , ITSN1 , in increasing Parkinson’s risk, especially when compared with variants in other well-established, genes such as , LRRK2 , and , GBA1,” Dhindsa said.
” We focus on rare genetic mutations because they often confer large effects on disease risk that reveal critical disease mechanisms. These genetic discoveries not only deepen our understanding of Parkinson’s biology but also unveil promising new targets for therapeutic intervention,” Dhindsa explained.
ITSN1 , plays an important role in how neurons send messages to each other– a process called synaptic transmission – making it particularly relevant to Parkinson’s disease, a condition in which disruption of nerve signals leads to the typical symptoms of impaired gait and balance, tremors and rigidity.
” We also showed in fruit flies that reducing , ITSN1 , levels worsens Parkinson ‘s-like features, including the ability to climb. We plan to extend these investigations to stem cell and mouse models,” Dhindsa said.
Interestingly, previous studies have recently implicated similar , ITSN1 , mutations in autism spectrum disorder ( ASD ). Other emerging data also have suggested an association between ASD and Parkinson’s disease, 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 highlights , ITSN1 , as a promising therapeutic target and underscores the value of large-scale genetic sequencing in identifying rare mutations that contribute to complex neurological disorders.
Others contributors to this work 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 Garg, Lawrence Middleton, Michal Tyrlik, Mirko Messa, Guillermo del Angel, Daniel G. Calame, Hiba Saade, Laurie Robak, Ben Hollis, Vishnu A Cuddapah, Huda Y. Zoghbi, Joshua M. Shulman, Slavé Petrovski, Ismael Al-Ramahi , and Ioanna Tachmazidou.
The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, AstraZeneca, the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Rice University and the University of Melbourne.
About this genetics and Parkinson’s disease research news
Author: Graciela Gutierrez
Source: Baylor College of Medicine
Contact: Graciela Gutierrez – Baylor College of Medicine
Image: The image is credited to Neuroscience News
Original Research: Open access.
” Haploinsufficiency of ITSN1 is associated with a substantial increased risk of Parkinson’s disease” by Ryan S. Dhindsa et al. Cell Reports
Abstract
Haploinsufficiency of ITSN1 is associated with a substantial increased risk of Parkinson’s disease
Despite its significant heritability, the genetic basis of Parkinson’s disease ( PD ) remains incompletely understood.
Here, in analyzing whole-genome sequence data from 3, 809 PD cases and 247, 101 controls in the UK Biobank, we discover that protein-truncating variants in , ITSN1 , confer a substantially increased risk of PD ( p , = , 6.1 , × , 10−7, odds ratio]95 % confidence interval ]  , = 10.5]5.2, 21.3] ).
We replicate this association in three independent datasets totaling 8, 407 cases and 413, 432 controls ( combined , p , = 4.5 , × , 10−12 ). Notably,  , ITSN1 , haploinsufficiency has also been associated with autism spectrum disorder, suggesting variable penetrance/expressivity.
In , Drosophila, we find that loss of the , ITSN1 , ortholog , Dap160 , exacerbates α-synuclein-induced neuronal toxicity and motor deficits, and , in , vitro , assays further suggest a physical interaction between ITSN1 and α-synuclein.
These results firmly establish , ITSN1 , as a PD risk gene with an effect size exceeding previously established loci, implicate vesicular trafficking dysfunction in PD pathogenesis, and potentially open new avenues for therapeutic development.
