Prion diseases are a group of progressive and fatal neurodegenerative disorders characterized by deposition of scrapie prion protein (PrPSc) in the CNS. This deposition is accompanied by neuronal loss, spongiform change, astrogliosis, and conspicuous microglial activation. Here, we argue that microglia play an overall neuroprotective role in prion pathogenesis. Several microglia-related molecules, such as Toll-like receptors (TLRs), the complement system, cytokines, chemokines, inflammatory regulators, and phagocytosis mediators, are involved in prion pathogenesis. However, the molecular mechanisms underlying the microglial response to prion infection are largely unknown. Consequently, we lack a comprehensive understanding of the regulatory network of microglial activation. On the positive side, recent findings suggest that therapeutic strategies modulating microglial activation and function may have merit in prion disease. Moreover, studies on the role of microglia in prion disease could deepen our understanding of neuroinflammation in a broad range of neurodegenerative disorders.
Adriano Aguzzi, Caihong Zhu
Guidelines: The Editorial Board will only consider letters that we deem relevant and of interest to our readers. We will not post data that have not been subjected to peer review, nor will we post letters that are essentially a reiteration of another letter. We reserve the right to edit any letter for length, content, and clarity. Authors will be notified by e-mail if their letters were accepted. No appeals will be considered.
Specific requirements: All letters must be 400 words or fewer. You may enter the letter as plain text or HTML. The author's name and e-mail address are required, and will be posted with the letter. All possible conflicts of interest must be noted, even if they are not posted. If you wish to include a figure (keep in mind that non-peer-reviewed data will not be posted), please contact the editors directly at editors@the-jci.org.