Immune activation in brain aging and neurodegeneration: too much or too little?

By Kurt M. Lucin, T. Wyss‐Coray. Neuron, 2009

662 citations recorded by the source corpus.

Until recently the brain was studied almost exclusively by neuroscientists and the immune system by immunologists, fuelling the notion that these systems represented two isolated entities. However, as more data suggest an important role of the immune system in regulating the progression of brain aging and neurodegenerative disease, it has become clear that the crosstalk between these systems can no longer be ignored and a new interdisciplinary approach is necessary. A central question that emerges is whether immune and inflammatory pathways become hyperactivated with age and promote degeneration or whether insufficient immune responses, which fail to cope with age-related stress may contribute to disease. We try to explore here the consequences of gain- versus loss-of-function with an emphasis on microglia as sensors and effectors of immune function in the brain and we discuss the potential role of the peripheral environment in neurodegenerative diseases.

Subfields: Biological Psychiatry, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/07c63efc9a46433f7f5de982c14e7d425e50d47d

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Citations in the corpus

Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases (2015, background): “More importantly, aged microglia are also manifested by altered inflammatory profiles [146].”
Microbiota Dysbiosis Controls the Neuroinflammatory Response after Stroke (2016, background): “…after stroke shown by us and others (Benakis et al., 2016) affects neuronal protection/toxicity directly or if it affects stroke outcome indirectly via microglial function, as was shown previously to occur by braininvading lymphocytes (Appel, 2009; Lucin and Wyss-Coray, 2009; Liesz et al., 2011).”
Reactive Astrocytes: Production, Function, and Therapeutic Potential. (2017, background): “…from peripheral immune cells and the vast array of cytokines and reactive oxygen species they release—the presence of which produces an inflammatory CNS environment that is at best correlative and at worst causative of neuroinflammatory insult and neurodegeneration (see Lucin and Wyss-Coray, 2009).”
TYROBP in Alzheimer’s Disease (2015, background): “In AD, the complement system is observed to initiate inflammatory reactions [42] in the CNS by upregulation of phagocytosis induced via activation and migration of immune cells [43].”
Neuroinflammation after traumatic brain injury: opportunities for therapeutic intervention. (2012, positive): “Aging also influences microglial activation (Conde and Streit, 2006b; Lucin and Wyss-Coray, 2009), and exacerbated microglial activation and astroglial responses to injury likely contribute to the enhanced susceptibility to and poor recovery from TBI in elderly patients (Galbraith, 1987; Pennings et”
Role of pro-inflammatory cytokines released from microglia in Alzheimer's disease. (2015, background): “Depending on their activation status and the encountered pathologic events, microglia are able to exert a variety of effecter functions, which may be either neurotoxic or neuroprotective (17).”
Immune modulation of learning, memory, neural plasticity and neurogenesis. (2011, neutral): “…neuroinflammation in driving AD pathology, a more complex picture has emerged, depicting inflammatory processes both as potent drivers of disease and as mediators of beneficial responses that reduce disease pathology (Lucin and Wyss-Coray, 2009; Schwartz et al., 2009; Shaftel et al., 2008).”
Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission (2011, background): “Actually, an increasing number of endogenous TLR ligands have now been described (81), and we speculate that the mechanisms that we have now deciphered will be relevant during physiological situations.”
Alzheimer’s Disease: The Challenge of the Second Century (2011, background): “It is likely that this inflammatory response contributes to brain injury, although there is evidence that glial cells also play a protective role (18, 19) (Fig.”