Peripheral inflammatory mediators in neurodegenerative diseases and their impact on disease progression

Il 18/12/2015 ore 14.30 - 15.30

Sala conferenze CNR, Via P. Castellino, 111 80131 Napoli

Dr. Paola Bossù will give a seminar on Alzheimer’s Disease (AD) that is an incurable and progressive neurodegenerative disturbance characterized by loss of brain neurons and leading to dementia. Microglia activation and brain neurotoxic inflammatory mediators are key components in AD pathogenic mechanisms, thus inflammation is a pathogenic process with promising target features for therapeutic improvement of the disease. However, the contribution of peripheral immunity in regulating AD neuroinflammation is still unclear in AD patients. Thus, they searched for blood cells and blood cell-associated molecules of the innate immune system as potential mediators and new candidate biomarkers in subjects affected by sporadic AD.

Dr Bossù's group found that two gene promoter polymorphisms of the pro-inflammatory cytokine IL-18 may predict risk and outcome of AD and that the expression of IL-18 and its receptor is increased in stimulated blood cells from AD patients, as compared to matched controls. The increased levels of cell-associated IL-18 in AD patients, partly dependent from genetic factors, are related to the severity of cognitive impairment. Interestingly, IL-18 production is also increased in human monocyte-derived DCs following a long-lasting stimulation with amyloid β, a key pathogenic factor of AD. In line with a possible role of DCs in AD, they demonstrated that monocyte-derived DCs are dysregulated in AD patients versus controls, since they display more pronounced pro-inflammatory phenotype, impaired ability to induce T-cell proliferation and reduced capacity to release neurotrophic factors. As a further confirmation of the possibility that DCs are indeed involved in neurodegeneration and recruited to degenerated brain as participants in neuroinflammation amplification, they observed a decline of myeloid DC precursors in blood of AD patients, occurring in association with increased severity of disease symptoms.

Overall, the reported findings argue for the involvement in AD of pro-inflammatory cytokines like IL-18, and the participation of regulatory immune cells like DCs, implicating that immune changes in the periphery are important areas for future research. In fact, despite the possible complexity of their roles in AD, peripheral immune mediators provide a new and important set of targets for a better understanding of disease pathogenesis and improvement of drug discovery approaches against this devastating and still uncontrollable brain illness.

Paola Bossù is a scientist with expertise in fundamental, industrial and clinical research in the field of inflammation and immunology. She is currently research director at the hospital-based research institute Santa Lucia Foundation in Rome. Her scientific interests are mainly focused to investigate within a clinical setting, the immune-inflammatory mechanisms involved in disabling brain diseases, like neurodegeneration.

Organizzato da:
IBP, Cnr

Referente organizzativo:
Diana Boraschi
CNR - Istituto di biochimica delle proteine
Via P. Castellino, 111 80131 Napoli
d.boraschi@ibp.cnr.it
081/6132623

Modalità di accesso: ingresso libero