NLRP3 inflammasome signalling in Alzheimer's disease.

Every year, 10 million people develop dementia, the most common of which is Alzheimer's disease (AD). To date, there is no way to prevent cognitive decline and therapies are limited. This review provides a neuroimmunological perspective on the progression of AD, and discusses the immune-targeted therapies that are in preclinical and clinical trials that may impact the development of this disease. Specifically, we look to the role of the NLRP3 inflammasome, its triggers in the brain and how its activation can contribute to the progression of dementia. We summarise the range of inhibitors targeting the NLRP3 inflammasome and its downstream pathways that are under investigation, and discuss future therapeutic perspectives for this devastating condition.

Disease mechanisms as subtypes: Immune dysfunction in Parkinson's disease.

In recent years, the contraposition between inflammatory and neurodegenerative processes has been increasingly challenged. Inflammation has been emphasized as a key player in the onset and progression of Parkinson disease (PD) and other neurodegenerative disorders. The strongest indicators of the involvement of the immune system derived from evidence of microglial activation, profound imbalance in phenotype and composition of peripheral immune cells, and impaired humoral immune responses. Moreover, peripheral inflammatory mechanisms (e.g., involving the gut-brain axis) and immunogenetic factors are likely to be implicated. Even though several lines of preclinical and clinical studies are supporting and defining the complex relationship between the immune system and PD, the exact mechanisms are currently unknown. Similarly, the temporal and causal connections between innate and adaptive immune responses and neurodegeneration are unsettled, challenging our ambition to define an integrated and holistic model of the disease. Despite these difficulties, current evidence is providing the unique opportunity to develop immune-targeted approaches for PD, thus enriching our therapeutic armamentarium. This chapter aims to provide an extensive overview of past and present studies that explored the implication of the immune system in neurodegeneration, thus paving the road for the concept of disease modification in PD.