Astrocytes and neuroinflammation in Alzheimer's disease

Abstract

Increased production of amyloid β-peptide (Aβ) and altered processing of tau in Alzheimer's disease (AD) are associated with synaptic dysfunction, neuronal death and cognitive and behavioural deficits. Neuroinflammation is also a prominent feature of AD brain and considerable evidence indicates that inflammatory events play a significant role in modulating the progression of AD. The role of microglia in AD inflammation has long been acknowledged. Substantial evidence now demonstrates that astrocyte-mediated inflammatory responses also influence pathology development, synapse health and neurodegeneration in AD. Several anti-inflammatory therapies targeting astrocytes show significant benefit in models of disease, particularly with respect to tau-associated neurodegeneration. However, the effectiveness of these approaches is complex, since modulating inflammatory pathways often has opposing effects on the development of tau and amyloid pathology, and is dependent on the precise phenotype and activities of astrocytes in different cellular environments. An increased understanding of interactions between astrocytes and neurons under different conditions is required for the development of safe and effective astrocyte-based therapies for AD and related neurodegenerative diseases.

Uncoupling protein 2 modulation of the NLRP3 inflammasome in astrocytes and its implications in depression

“…Recently, animal studies and postmortem brain analyses of patients with depression implicated glial dysfunction in MDD pathophysiology [43], [44]. Astrocytes-mediated inflammation plays an important role in the pathogenesis of depression [45] and neurodegenerative diseases such as Alzheimer Disease [46], Parkinson Disease [27] and stroke [47]. UCP2 knockout enhanced the activation of NLRP3 inflammasome and increased the production of IL-1β in astrocytes, indicating that astrocytic UCP2 is involved in the development of the NLRP3 inflammasome-driven inflammatory diseases, including depression.…”

Insulin resistance and cognitive dysfunction

“…The inflammatory reaction is a core pathological mechanism of AD [83][84][85]. Inflammatory responses, which are present in obesity and T2DM, are closely related to the development of IR in both peripheral and central tissues, thus may increase the risk of AD [86].…”

Electric stimulation of the vagus nerve reduced mouse neuroinflammation induced by lipopolysaccharide

“…These findings, together with the use of VNS in humans to treat refractory partial-onset seizures and severe recurrent refractory depression, give rise to great expectations on its use to ameliorate chronic NI and to contribute to the control of the progression of neurodegenerative diseases [28–30]. …”