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Glial cell dysregulation: a new perspective on Alzheimer disease

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Abstract

Alzheimer disease (AD) is a major cause of dementia. Several mechanisms have been postulated to explain its pathogenesis, beta-amyloid (Aß toxicity, cholinergic, dysfunction, Tau hyperphosphorylation, oxidative damage, synaptic dysfunction and inflammation secondary to senile plaques, among others. Glial cells are the major producers of inflammatory mediators, and cytotoxic activation of glial cells is linked to several neurodegenerative diseases; however, whether inflammation is a consequence or the cause of neurodegeneration is still unclear. I propose that inflammation and cellular stress associated with aging are key events in the development of AD through the induction of glial dysfunction. Dysregulated inflammatory response can elicit glial cell activation by compounds which are normally poorly reactive. Inflammation can also be the major cause of defective handling of Aß and the amyloid precursor protein (APP). Here I review evidence that support the proposal that dysfunctional glia and the resulting neuroinflammation can explain many features of AD. Evidence supports the notion that damage caused by inflammation is not only a primary cause of neurodegeneration but also an inducer for the accumulation of Aß in AD. Dysfunctional glia can result in im paired neuronal function in AD, as well as in many progressive neurodegenerative disorders. We show that microglial cell activation is enhanced under pro-inflammatory conditions, indicating that glial cell responses to Aß related proteins can be critically dependent on the priming of glial cells by pro-inflammatory factors.

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    Rommy Von Bernhardi

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Von Bernhardi, R. Glial cell dysregulation: a new perspective on Alzheimer disease. neurotox res 12, 215–232 (2007). https://doi.org/10.1007/BF03033906

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