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Neurodegenerative disorders: The Glia way forward

DOI: 10.3389/fphar.2014.00157

Keywords: Immunity, Inflammation, Neurodegenerative disorders, Therapeutics, Animal Models

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Abstract:

The realisation that inflammation can affect the brain is not a new one, and many diseases of the CNS, such as multiple sclerosis (MS), have been shown to clearly respond to agents that target the immune system at one level or another. However it is only more recently that the immune system has been shown to play a role in the normal development and homeostasis of the brain as well as contributing to disorders that have traditionally been thought of as being purely neurodegenerative in nature, such as Huntington’s (HD) or Alzheimer’s disease (AD). In this special issue of Frontiers in Neuropharmacology, we have sought to bring together experts in this new emerging area of neurobiology. The best place to start in this special issue is with the paper by Patrick and Edith McGeer as they lay out the history of the field and the scepticism that it has generated en route, and which still exists today. Indeed many neurologists and neurobiologists still argue that any inflammatory or glial response in neurodegenerative disorders is simply a secondary phenomenon of no pathogenic or therapeutic relevance. However, evidence has accumulated in favour of it having a role and part of this relates to our ability to better image the microglial responses in patients with neurodegenerative disorders of the brain and Marios Politis, Paul Su and Paola Piccini explore this in their review on PET and TSPO radioligands. A number of our papers summarise the role of microglia in ongoing CNS activities. Christine Ekdahl, for example, discusses how microglia may regulate adult neurogenesis in the healthy and diseased brain possibly through direct synaptic contacts. This is taken on by Wolfgang Streit and Qing-Shan Xue who put forward the theory that the loss of the normal neuroprotective function of microglial, as a result of aging, leads to disease states, especially AD. Jonas Neher, Urte Neniskyte and Guy Brown, on the other hand, discuss how microglia can directly phagocyte apparently healthy neurons as well as those in the diseased brain and by so doing are primary players in the cell loss seen in neurodegenerative disorders. This is explored in more detail by Sudarshan Phani Diane Re and Serge Przedborski in Ayotrophic Lateral Sclerosis (ALS); Egle Solito and Magdalena Sastre in AD; and Yue Huang and Glenda Halliday for Parkinson’s disease (PD). Finally in the first of our two reviews, we discuss how the astrocytic and microglial responses are different in a range of new experimental therapies for neurodegenerative disorders. These therapies include chronic deep brain

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