On the reactive states of astrocytes in prion diseases

ABSTRACT

Transformation of astrocytes into reactive states is considered one of the major pathological hallmarks of prion and other neurodegenerative diseases. Recent years witnessed a growing appreciation of the view that reactive astrocytes are intimately involved in chronic neurodegeneration; however, little is known about their role in disease pathogenesis. The current article reviews the progress of the last few years and critically discusses controversial questions of whether reactive astrocytes associated with prion diseases are neurotoxic or neuroprotective and whether bidirectional A1–A2 model is applicable for describing polarization of astrocytes. Moreover, other important topics, including reversibility of a transition to a reactive state, along with the role of microglia and other stimuli in triggering astrocyte activation are reviewed. Defining the role of reactive astrocytes in pathogenesis of neurodegenerative diseases will open unrealized opportunities for developing new therapeutic approaches against prion and other neurodegenerative diseases.

KEYWORDS:

• Prion
• prion diseases
• reactive astrocytes
• reactive microglia

Acknowledgments

We thank Kara Molesworth for editing this manuscript. This work was supported by NIH grants NS045585 and AI128925.

Disclosure of potential conflicts of interest

No potential conflict of interest was reported by the author(s).

Abbreviations

PrP^C, normal cellular isoform of the prion protein; PrP^Sc, abnormal, disease-associated isoform of the prion protein

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Additional information

Funding

This work was supported by the National Institute of Allergy and Infectious Diseases [AI128925]; National Institute of Neurological Disorders and Stroke [NS045585].