Highlights •Lack of neuronal IFN-β-IFNAR signaling causes brain Lewy body accumulation •IFN-β deficiency causes late-stage autophagy block and thereby α-synuclein aggregation •IFN-β promotes neuronal autophagy and α-synuclein clearance •Ifnb gene therapy prevents dopaminergic neuron loss in a familial PD model
Non-inheritable PD may be caused by functional changes in the immune regulating gene Interferon-beta. Treatment with Interferon-beta-gene therapy successfully prevented neuronal death and disease effects in an experimental model of PD.
7-10 million people worldwide are living with PD. More than half of PD patients develop progressive disease showing signs of dementia similar to Alzheimer’s disease. The human brain consists of approximately 100 billion neurons, which coordinate activities in all parts of the body.
“We found that IFNβ is essential for neurons ability to recycle waste proteins. Without this, the waste proteins accumulate in Lewy bodies and with time the neurons die,” explains assistant professor Patrick Ejlerskov. The research team found that mice missing IFNβ developed Lewy bodies in parts of the brain, which control body movement and restoration of memory, and as a result they developed disease and clinical signs similar to patients with PD and dementia with Lewy bodies (DLB).
While hereditary gene mutations have long been known to play a role in familial PD, the study from BRIC offers one of the first models for so-called non-familial PD, which comprises the majority (90-95%) of patients suffering from PD. According to professor Shohreh Issazadeh-Navikas the new knowledge opens new therapeutic possibilities:
“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. It is independent of gene mutations known from familial PD and when we introduced IFNβ-gene therapy, we could prevent neuronal death and disease development. Our hope is that this knowledge will enable development of more effective treatment of PD,” says professor Shohreh Issazadeh-Navikas. http://www.bric.ku.dk/selected-publications/immune-gene-prevents-parkinsons-disease-and-dementia/
Recent Comments