**Neuroinflammation and Neurodegeneration**

Inelia Morales, Gonzalo A. Farías, Nicole Cortes and Ricardo B. Maccioni

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/64545

#### **Abstract**

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Csid=b172d9ebb2bfdf1ed18a4f1ef5ac71b6.

Pathophysiological processes of neurodegenerative diseases are not clearly defined. However, an important body of evidence points toward the role of various inflamma‐ tory processes. The microglial cell is the main representative of the immune system in the central nervous system (CNS). This cell type can sense foreign or harmful patho‐ gens and trigger its own activation and the generation of neuroinflammatory process‐ es through phagocytosis and the release of cytokines, in order to maintain the cellular microenvironment. However, after maintaining a permanent state of activation due to sustained stimulation over time, microglial cells may generate a focus of persistent inflammation that in some cases precedes or enhances the neurodegenerative process. Thus, neuroinflammatory microenvironment becomes toxic and harmful for the neuronal cell, which degenerates and releases various factors that in turn activate the inflammatory response of microglia, potentiating the neurodegenerative cycle. In this chapter, we discuss the evidence on the role of microglial cell activation in neurodege‐ nerative conditions and the association between neuroinflammatory processes and agerelated neurological diseases. Finally, we outline how this new approach can help us to find new ways to understand neurodegenerative processes and to orientate the search for new therapies.

**Keywords:** neuroinflammation, neurodegeneration, Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, microglia, neuroimmunomodulation hypothe‐ sis, inflammatory response

#### **1. Introduction**

Neurodegeneration is a degenerative process that occurs in the central nervous system (CNS), in which an injury or deleterious condition detonates progressive neuronal death, leading to

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the loss of cognitive and motor functions associated with the CNS. The causes that trigger this neuronal death are still unknown, but clinical evidence demonstrates that age is an impor‐ tant risk factor and that the number of people suffering from dementia and other neurodege‐ nerative conditions will increase as a consequence of increased life expectancies [1]. The main diseases that are defined by neurodegenerative processes are: AD and PD, but this term also includes other conditions such as amyotrophic lateral sclerosis (ALS), multiple sclerosis and products of viral infections. These diseases have an impact not only on the individual suffering from the disease but also on their families, causing social isolation, family misunderstand‐ ing, and loss of friendships and social ties [2]. This is an important issue and should be further considered, especially because itis currently estimated that 94% of people living with dementia are cared for at home, generating an important amount of distress and economic burden on their closest relatives. This is particularly true for many low- and middle-income countries, where in many cases patients and caregivers have access only to limited support from the state and health providers.

According to epidemiological data from the "World Alzheimer Report 2015" [3], there are more than 46 million people with dementia worldwide, and it is estimated that this number will increase to 131.5 million by 2050. Moreover, it is also important to consider that this type of disease carries a huge economic impact. Currently, only AD monetarily translates in US \$818 million per year globally and is estimated to be billions of dollars by 2018 [3]. This amount will certainly rise significantly if we consider other neurodegenerative diseases mentioned above. The reasons that trigger neurodegenerative processes in these diseases remain unclear, especially considering the many variables that are involved in their development. One of these variables, inflammation, became more relevant in recent years. One example is the evidence that exists today on neurodegeneration induced by viral infections [1, 4], as it involves the interaction of the CNS, environmental factors, and immune response. In parallel there are also studies that link the rising number of mild proinflammatory conditions described with major degenerative diseases of the elderly [5]. Thus, the major pathologies, associated with aging and increased physical frailty, are also associated with changes in body composition, energy imbalance, homeostatic dysregulation, and neurodegeneration. Chronic inflammation is strongly connected to each of these aging phenotypes [6].

The inflammatory response is triggered to fight and control an injury, infection or other stimulus and may involve many cell types. The impact of the response is dependent on the numerous factors secreted by these cells, and they have the ability to self-regulate their response in order to repair tissue damage and to eliminate pathogenic elements. But when the response is prolonged in time, it causes a chronic inflammatory environment that leads to progressive tissue damage [6]. One of the evidences that support the relation between inflammation and increasing age is given by the increase in inflammatory mediators IL-6 and IL-8 and the rise in C-reactive protein in men and women with age, and the fact that these values also increase in obesity and neurodegenerative diseases [7].

In this chapter, we present a complete summary of the neuroinflammatory process and we explain how it relates to the development of features of neurodegeneration and neuronal death as in dementia neuropathology. We describe the neuroinflammatory processes considering microglial cell as the main cell type involved in the development of the immune response in the CNS. Finally, we link the development of the immune response to long-term development of three of the most characteristic diseases related to neurodegenerative diseases: AD, PD and ALS.
