Study first to link immunogenetics to non-familial Parkinson’s disease.
An estimated seven to ten million people worldwide are living with Parkinson’s disease (PD), which is an incurable and progressive disease of the nervous system affecting movement and cognitive function. More than half of PD patients develop progressive disease showing signs of dementia similar to Alzheimer’s disease. Protein aggregates which eventually form larger Lewy bodies, are seen in PD, dementia with Lewy bodies, multiple system atrophy, and in some forms of Alzheimer’s disease; showing that neurodegenerative diseases associated with aging have disrupted neuronal homeostasis whose pathologies often overlap.
Neurodegenerative events in these diseases are linked to inflammation, however, despite this link, defects in genes regulating inflammation do not have an established causative role in neurodegeneration. Now, a study from researchers team at University of Copenhagen shows that non-familial PD may be caused by functional changes in the immune regulating gene Interferon-beta (IFNβ). The team state that treatment with IFNβ-gene therapy successfully prevented neuronal death and disease effects in an experimental model of PD. The opensource study is published in the journal Cell.
Previous studies show that IFNβ belongs to the type I interferon family of cytokines and binding to its receptor, interferon-α/β receptor (IFNAR), results in immunoregulation including anti-viral and anti-inflammatory effects and benefits for multiple sclerosis patients. However, the role of IFNβ in classic neurodegenerative diseases is unknown. The current study shows that deletion of IFNβ is sufficient to cause a cascade of neurodegenerative events.
The current study used IFNβ knockout mice with spontaneous pathologies mimicking major aspects of human neurodegeneration such as PD and DLB to show that the immune gene IFNβ plays a vital role in keeping neurons healthy. Data findings show that IFNβ is essential for neurons to recycle waste proteins. The researchers explain that without this recycling system, the waste proteins accumulate in the disease-associated structures, Lewy bodies, and with time the neurons die. The team observed that mice missing IFNβ, developed Lewy bodies in parts of the brain which control body movement and restoration of memory, and as a result developed pathology similar to patients with PD and dementia with Lewy bodies.
The group state that this is one of the first genes found to cause pathology and clinical features of non-familial PD and DLB, through accumulation of disease-causing proteins. They go on to add that it is independent of gene mutations known from familial PD and when an IFNβ-gene therapy was introduced neuronal death and disease development was prevented. The lab conclude that while hereditary gene mutations have long been known to play a role in familial PD, their findings offer one of the first models for non-familial PD, which comprises the majority (90-95%) of patients suffering from PD.
The team surmise that current treatments are effective at improving the early motor symptoms of the disease, however, as the disease progress, the treatment effect is lost. They go on to add that they hope is that their findings will enable development of more effective treatment of PD. For the future, the researchers plan to gain a better understanding of the molecular mechanisms by which IFNβ protects neurons and thereby prevents movement disorders and dementia.
Source: University of Copenhagen
aging, dementia, genetics, healthinnovations, immune response, immunogenetics, immunology, inflammation, interferon beta, neurodegeneration, neurogenetics, neuroinflammation, neuroinnovations, opensource, Parkinson's disease
Michelle Petersen View All
Michelle is a health industry veteran who taught and worked in the field before training as a science journalist.
Featured by numerous prestigious brands and publishers, she specializes in clinical trial innovation--expertise she gained while working in multiple positions within the private sector, the NHS, and Oxford University.
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