The role of microglia in prion diseases and possible therapeutic targets: a literature review

Author(s)

Lamenha Falcao de Melo, Ananda Sampaio ^[1] ; Dias Lima, Juliana Louise ^[1] ; Silva Malta, Maria Carolina ^[1] ; Marroquim, Natalia Franca ^[1] ; Moreira, Alvaro Rivelli ^[2] ; Ladeia, Isabelle de Almeida ^[2] ; Cardoso, Fabrizio dos Santos ^{[3, 4, 5]} ; Goncalves, Daniel Buzaglo ^[6] ; Dutra, Bruna Guimaraes ^[6] ; Claudino dos Santos, Julio Cesar ^[7]

Affiliation

^[1] Univ Fed Alagoas, Fac Med, Alagoas, AL - Brazil

^[2] UniFacog, Dept Neurol, Ctr Univ Governador Ozanam Coelho, Uba, MG - Brazil

^[3] Univ Mogi das Cruzes, Nucleo Pesquisas Tecnol, Mogi Das Cruzes, SP - Brazil

^[4] Univ Texas Ut, Dept Psychol, Austin, TX - USA

^[5] Univ Texas Ut, Inst Neurosci, Austin, TX - USA

^[6] Univ Fed Amazonas, Uba, Amazonas - Brazil

^[7] Univ Fed Sao Paulo, Dept Neurol E Neurocirurgia, Lab Neurociencias, Sao Paulo, SP - Brazil

• Document type: Review article
• Source: PRION; v. 15, n. 1, p. 191-206, JAN 1 2021.
• Web of Science Citations: 0

Abstract

Creutzfeldt-Jakob disease (CJD) is a rare and fatal condition that leads to progressive neurodegeneration due to gliosis, vacuolation of central nervous system tissue, and loss of neurons. Microglia play a crucial role in maintaining Central Nervous System (CNS) homoeostasis, both in health and disease, through phagocytosis and cytokine production. In the context of CJD, the immunomodulatory function of microglia turns it into a cell of particular interest. Microglia would be activated by infectious prion proteins, initially acquiring a phagocytic and anti-inflammatory profile (M2), and producing cytokines such as IL-4, IL-10, and TGF-beta. Therefore, microglia are seen as a key target for the development of new treatment approaches, with many emerging strategies to guide it towards a beneficial role upon neuroinflammation, by manipulating its metabolic pathways. In such a setting, many cellular targets in microglia that can be involved in phenotype modulation, such as membrane receptors, have been identified and pointed out as possible targets for further experiments and therapeutic approaches. In this article, we review the major findings about the role of microglia in CJD, including its relationship to some risk factors associated with the development of the disease. Furthermore, considering its central role in neural immunity, we explore microglial connection with other elements of the immune system and cell signalling, such as inflammasomes, the complement and purinergic systems, and the latest finding strategies to guide these cells from harmful to beneficial roles. (AU)

• FAPESP's process: 17/16443-0 - Therapeutic potential of low-level laser in the brain of aged rats
• Grantee: Fabrízio dos Santos Cardoso
• Support Opportunities: Scholarships in Brazil - Doctorate