The Role of Macrophages in Neuroinflammatory and Neurodegenerative Pathways of Alzheimer's Disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis: Pathogenetic Cellular Effectors and Potential Therapeutic Targets

Santa Mammana, Paolo Fagone, Eugenio Cavalli, Maria Sofia Basile, Maria Cristina Petralia, Ferdinando Nicoletti, Placido Bramanti, Emanuela Mazzon

Research output: Contribution to journalReview articlepeer-review

Abstract

In physiological conditions, different types of macrophages can be found within the central nervous system (CNS), i.e., microglia, meningeal macrophages, and perivascular (blood-brain barrier) and choroid plexus (blood-cerebrospinal fluid barrier) macrophages. Microglia and tissue-resident macrophages, as well as blood-borne monocytes, have different origins, as the former derive from yolk sac erythromyeloid precursors and the latter from the fetal liver or bone marrow. Accordingly, specific phenotypic patterns characterize each population. These cells function to maintain homeostasis and are directly involved in the development and resolution of neuroinflammatory processes. Also, following inflammation, circulating monocytes can be recruited and enter the CNS, therefore contributing to brain pathology. These cell populations have now been identified as key players in CNS pathology, including autoimmune diseases, such as multiple sclerosis, and degenerative diseases, such as Amyotrophic Lateral Sclerosis and Alzheimer's disease. Here, we review the evidence on the involvement of CNS macrophages in neuroinflammation and the advantages, pitfalls, and translational opportunities of pharmacological interventions targeting these heterogeneous cellular populations for the treatment of brain diseases.

Original languageEnglish
Pages (from-to)1-20
Number of pages19
JournalInternational Journal of Molecular Sciences
Volume19
Issue number3
DOIs
Publication statusPublished - Mar 13 2018

Keywords

  • Alzheimer Disease/drug therapy
  • Amyotrophic Lateral Sclerosis/drug therapy
  • Animals
  • Central Nervous System/metabolism
  • Humans
  • Macrophages/metabolism
  • Molecular Targeted Therapy
  • Multiple Sclerosis/drug therapy

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