RESUMO
Alzheimer's disease (AD) is the main cause of dementia worldwide. The definitive diagnosis of AD is clinicopathological and based on the identification of cerebral deposition of Amyloid ß (Aß) plaques and neurofibrillary tangles. However, the link between amyloid cascade and depositions of phosphorylated tau (p-tau) is still missing. In this scenario, inflammasomes might play a relevant role. Experimental models of AD have suggested that Aß accumulation induces, through microglia, activation of the NLRP3 inflammasome. This activation contributes to the dissemination of Aß and p-tau, as well as to hyperphosphorylation of tau. Also, in experimental models, NLPR1 promoted neuronal pyroptosis. There are neither comprehensive neuropathologic characterization nor clinicopathologic studies evaluating the NLRP1 and NLRP3 inflammasomes in subjects with AD. The current mini-review aims to summarize recent and promising findings on the role of NLRP1 and NLRP3 signaling in the pathophysiology of AD. We also sought to highlight the knowledge gap in patients with AD, mainly the lack of clinicopathologic studies on the interaction among inflammasomes, Aß/tau pathology, and cognitive decline.
Assuntos
Doença de Alzheimer/metabolismo , Inflamassomos/metabolismo , Inflamação/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas NLR/metabolismo , Humanos , Transdução de SinaisRESUMO
Hyper activation of the neuroimmune system is strongly related to the development of neuropsychiatric disorders. Psychosocial stress has been postulated to play an important role in triggering anxiety and major depression. In preclinical models, there is mounting evidence that social defeat stress activates microglial cells in the central nervous system. This type of stress could be one of the major factors in the development of these psychopathologies. Here, we reviewed the most recent literature on social defeat and the associated immunological reactions. We focused our attention on microglial cells and kept the effect of social defeat over microglia separate from the effect of this stressor on other immune cells and the influence of peripheral immune components in priming central immune reactions. Furthermore, we considered how social defeat stress affects microglial cells and the consequent development of anxiety- and depressive-like states in preclinical studies. We highlighted evidence for the negative impact of the over-activation of the neuroimmune system, especially by the overproduction of pro-inflammatory mediators and cytotoxins. Overproduction of these molecules may cause cellular damage and loss or decreased function of neuronal activity by excessively pruning synaptic connections that ultimately contribute to the development of anxiety- and depressive-like states.
RESUMO
Today, there is enormous progress in understanding the function of glial cells, including astroglia, oligodendroglia, Schwann cells, and microglia. Around 150 years ago, glia were viewed as a glue among neurons. During the course of the twentieth century, microglia were discovered and neuroscientists' views evolved toward considering glia only as auxiliary cells of neurons. However, over the last two to three decades, glial cells' importance has been reconsidered because of the evidence on their involvement in defining central nervous system architecture, brain metabolism, the survival of neurons, development and modulation of synaptic transmission, propagation of nerve impulses, and many other physiological functions. Furthermore, increasing evidence shows that glia are involved in the mechanisms of a broad spectrum of pathologies of the nervous system, including some psychiatric diseases, epilepsy, and neurodegenerative diseases to mention a few. It appears safe to say that no neurological disease can be understood without considering neuron-glia crosstalk. Thus, this book aims to show different roles played by glia in the healthy and diseased nervous system, highlighting some of their properties while considering that the various glial cell types are essential components not only for cell function and integration among neurons, but also for the emergence of important brain homeostasis.