Neuroglia in neurodegeneration: Alzheimer, Parkinson, and Huntington disease.

Abstract

The conspicuous rise of chronic neurodegenerative diseases, including Alzheimer (AD), Parkinson (PD), and Huntington (HD) diseases, is currently without disease-modifying therapies and accompanied by an excessive rate of unsuccessful clinical trials. This reflects a profound lack of understanding of the pathogenesis of these diseases, indicating that the current paradigms guiding disease modeling and drug development are in need of reconsideration. The role of neuroglia, namely astrocytes, microglial cells, and oligodendrocytes, in the pathogenesis of neurodegenerative diseases emerged during the last decades. This chapter provides the state-of-the-art update on the changes of astrocytes, microglial cells, and oligodendrocytes in AD, PD, and HD. A growing body of evidence suggests that homeostatic and defensive functions of glial cells are compromised at different disease stages, leading to increased susceptibility of neurons to noxious stimuli, eventually resulting in their malfunction and degeneration. Investments are needed in the generation of novel preclinical models suitable for studying glial pathology, in "humanizing" research, and in-depth investigation of glial cell alterations to slow down and, possibly, halt and prevent the rise of neurodegenerative disease. Targeting glial cells opens new therapeutic avenues to treat AD, PD, and HD.