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 MammanaPaolo FagoneEugenio CavalliMaria Sofia BasileMaria Cristina PetraliaFerdinando NicolettiPlacido BramantiEmanuela MazzonPublished in: International journal of molecular sciences (2018)
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.
Keyphrases
- blood brain barrier
- amyotrophic lateral sclerosis
- multiple sclerosis
- cerebral ischemia
- cerebrospinal fluid
- bone marrow
- white matter
- inflammatory response
- oxidative stress
- induced apoptosis
- resting state
- single cell
- stem cells
- traumatic brain injury
- dendritic cells
- functional connectivity
- brain injury
- drug delivery
- cell proliferation
- cell cycle arrest
- peripheral blood
- single molecule
- ultrasound guided
- immune response
- mild cognitive impairment
- endoplasmic reticulum stress
- subarachnoid hemorrhage
- smoking cessation
- human health
- replacement therapy
- quality improvement