Inflammation in CNS neurodegenerative diseases

Abstract

Neurodegenerative diseases, the leading cause of morbidity and disability, are gaining increased attention as they impose a considerable socioeconomic impact, due in part to the ageing community. Neuronal damage is a pathological hallmark of Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, Huntington's disease, spinocerebellar ataxia and multiple sclerosis, although such damage is also observed following neurotropic viral infections, stroke, genetic white matter diseases and paraneoplastic disorders. Despite the different aetiologies, for example, infections, genetic mutations, trauma and protein aggregations, neuronal damage is frequently associated with chronic activation of an innate immune response in the CNS. The growing awareness that the immune system is inextricably involved in shaping the brain during development as well as mediating damage, but also regeneration and repair, has stimulated therapeutic approaches to modulate the immune system in neurodegenerative diseases. Here, we review the current understanding of how astrocytes and microglia, as well as neurons and oligodendrocytes, shape the neuroimmune response during development, and how aberrant responses that arise due to genetic or environmental triggers may predispose the CNS to neurodegenerative diseases. We discuss the known interactions between the peripheral immune system and the brain, and review the current concepts on how immune cells enter and leave the CNS. A better understanding of neuroimmune interactions during development and disease will be key to further manipulating these responses and the development of effective therapies to improve quality of life, and reduce the impact of neuroinflammatory and degenerative diseases.

Melatonin and inflammation—Story of a double‐edged blade

“…This is particularly evident in the most severe forms of dementias such as Alzheimer's disease (AD). Nevertheless, neuroinflammation is also a characteristic of other diseases of entirely different etiologies, such as Huntington’ disease, Parkinson's disease, amyotrophic lateral sclerosis, spinocerebellar ataxia, and multiple sclerosis . Inflammation leads necessarily to oxidative stress and, under conditions of strongly elevated NO levels, to nitrosative/nitrative stress, too.…”

CD93 regulates central nervous system inflammation in two mouse models of autoimmune encephalomyelitis

“…The perpetuation of an uncontrolled innate immune response in the central nervous system (CNS) is an inherent risk because the subsequent local inflammation may cause collateral tissue damage with necrosis, possibly leading to autoimmunity . Hence, non‐resolving inflammation is a major driver of chronic diseases including Alzheimer's disease as well as multiple sclerosis, as exemplified in several experimental autoimmune encephalomyelitis (EAE) mouse models …”

“…1 Hence, non-resolving inflammation is a major driver of chronic diseases including Alzheimer's disease as well as multiple sclerosis, as exemplified in several experimental autoimmune encephalomyelitis (EAE) mouse models. 2,3 Innate immune complement proteins and other soluble pattern recognition receptors have the ability to recognize equally pathogen-associated molecular patterns and hostderived damage-associated molecular patterns (DAMPs or alarmins). 4,5 It is critical that this initial recognition event signals appropriate effector-function responses with the phagocytosis of the debris but in a non-phlogistic manner.…”

How T'reg‐ulate healing of the injured spinal cord?

“…Tregs have been described as protective, inhibiting damaging inflammatory responses in models of stroke . There is evidence they may also be protective in models of immune‐mediated neuro‐degeneration, and in humans with amyotrophic lateral sclerosis . However, Tregs have also been shown to inhibit repair‐ and healing‐promoting adaptive and innate type 2 responses, thus potentially worsening secondary damage after neuronal injury in a model of ischaemic stroke.…”