Summary: A new study identified genetic variation in the ITSN1 gene that significantly increases the risk of developing Parkinson’s disease. Researchers analyzed nearly 500,000 genetic profiles and found that individuals with that n1 variant were up to 10 times more risk of Parkinson’s disease.
In this study, ITSN1 was linked to previous disease development and impaired neural signaling, which is essential for movement and coordination. Fruit fly experiments have shown that reducing its N1 levels exacerbate Parkinsons-like symptoms and its role in disease progression.
Interestingly, similar mutations in ITSN1 are associated with autism spectrum disorder, suggesting a potential link between ASD and Parkinson’s disease. These findings highlight ITSN1 as a promising target for future treatments.
Important Facts:
Genetic risk factors: ITSN1 gene mutants increase Parkinson’s risk up to 10 times. Neuronal Influence: ITSN1 plays an important role in synaptic transmission and affects movement.
Source: Baylor College of Medicine
A new study published in Cell Reports reveals groundbreaking findings linking genetic variants of the gene ITSN1 to a significant increase in the risk of Parkinson’s disease. This is a neurodegenerative condition affecting nearly 2% of adults over the age of 65.
The work, led by AstraZeneca, a team of researchers at Baylor College of Medding and the Yanduncan Neurological Institute at Texas Children’s Hospital, could pave the way for new treatments aimed at slowing or preventing the progression of Parkinson’s disease.
“Parkinson’s disease, the second most common neurodegenerative disorder, has no treatment yet.
“To address this unmet need, we analyzed genetic data from nearly half a million UK biobank participants and found that individuals carrying rare ITSN1 altered variants that impair the normal function of their genes face a 10-fold risk of developing Parkinson’s disease,” the Institute at the Children’s Hospital of Texas.
These findings were subsequently validated in three independent cohorts, including over 8,000 cases and 400,000 controls. Importantly, ITSN1 carriers became prevalent towards the early onset of illness.
“What makes this finding very important is the exceptional magnitude of the effect of ITSN1 in increasing risk of Parkinson’s disease, especially when compared to variants of other established genes such as LRRK2 and GBA1,” says Dhindsa.
“We focus on rare genetic variation because they often have a significant impact on disease risk, revealing important disease mechanisms. These genetic findings not only enhance our understanding of Parkinson’s disease biology, but also reveal new targets for therapeutic interventions,” Dhindsa explained.
ITSN1 plays an important role in the way neurons send messages to each other (a process known as synaptic transmission). It is particularly related to Parkinson’s disease. This is a condition in which the destruction of neural signals leads to the typical symptoms of walking and balance, balance, trembling and stiffness.
“We have also shown that reducing its n1 levels will exacerbate Parkinson-like characteristics, such as climbing ability. We plan to extend these studies to stem cell and mouse models,” Dhindsa said.
Interestingly, previous studies have recently involved similar ITSN1 mutations in autism spectrum disorder (ASD). Other emerging data also suggest a link between ASD and Parkinson’s disease, indicating that people with ASD are three times more likely to develop Parkinsonism.
“Our findings support future research to better understand the relationship between these two conditions and their associated mechanisms,” Dhindsa said.
This study highlights ITSN1 as a promising therapeutic target and highlights the value of large-scale genetic sequencing in identifying rare mutations that contribute to complex neurological disorders.
Other contributors to this work include Thomas P. Spargo, Chloe F. Sands, Isabella R. Juan, Jonathan Mitchell, Vidaravammer, Jessica C. Guillermo del Angel, Daniel G. Carame, Hiba Saad, Laurie Robach, Ben Hollis, Vishnu a Kuddapa, Huda Y. Zogbi, Joshua M. Schulman, Slave Petrovsky, Ismael al-Ramahi and Ionna Touchmajidou.
The authors are affiliated with one or more institutions, including Texas Children’s Hospital, Rice University, Baylor College at the University of Melbourne, AstraZeneca, AstraZeneca, AstraZeneca, and Dunduncan Neurological Institute.
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: Image credited to Neuroscience News
Original research: Open access.
“Haploinsufficiency in ITSN1 is associated with a significant increase in risk of Parkinson’s disease,” Ryan S. Dihdsa et al. Cell Report
Abstract
Haploinsufficiency in ITSN1 is associated with a significant increase in the risk of Parkinson’s disease
Despite its important hereditary nature, the genetic basis of Parkinson’s disease (PD) remains incompletely understood.
Here, we find that protein course variants of ITSN1 significantly increase the risk of PD when analyzing whole-genome sequence data from 3,809 PD cases and 247,101 controls from the UK biobank (P = 6.1 × 10-7;
This association reproduces a total of 8,407 cases and 413,432 controls in three independent datasets (P = 4.5×10-12 combination). In particular, ITSN1 haploinsufficiency is also associated with autism spectrum disorder, suggesting a variety of penetration/expressive powers.
In Drosophila, loss of the ITSN1 ortholog DAP160 exacerbates α-synuclein-induced neuronal toxicity and motor impairment, and in vitro assays further suggest a physical interaction between ITSN1 and α-synuclein.
These results solidly establish ITSN1 as a PD risk gene with an effect size exceeding previously established loci, which could involve vesicle transport dysfunction in the pathogenesis of PD, paving a new pathway for therapeutic development.
