Src family kinases (SFKs): critical regulators of microglial homeostatic functions and neurodegeneration in Parkinson's and Alzheimer's diseases. (4th October 2021)

• Record Type: Journal Article
• Authors: Portugal, Camila C.; Almeida, Tiago O.; Socodato, Renato; Relvas, João B.
• Is Part Of: FEBS journal. Volume 289:Number 24(2022)
• Page Start: 7760
• Page End: 7775
• Publication Date: 2021-10-04
• Subjects: alpha‐synuclein -- amyloid -- cytoskeleton -- glia and synapse -- migration -- NF‐kB -- phagocytosis -- proliferation -- RhoGTPase -- ROS; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.16197
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : c‐Src was the first protein kinase to be described as capable of phosphorylating tyrosine residues. Subsequent identification of other tyrosine‐phosphorylating protein kinases with a similar structure to c‐Src gave rise to the concept of Src family kinases (SFKs). Microglia are the resident innate immune cell population of the CNS. Under physiological conditions, microglia actively participate in brain tissue homeostasis, continuously patrolling the neuronal parenchyma and exerting neuroprotective actions. Activation of pathogen‐associated molecular pattern (PAMP) and damage‐associated molecular pattern (DAMP) receptors induces microglial proliferation, migration toward pathological foci, phagocytosis, and changes in gene expression, concurrent with the secretion of cytokines, chemokines, and growth factors. A significant body of literature shows that SFK stimulation positively associates with microglial activation and neuropathological conditions, including Alzheimer's and Parkinson's diseases. Here, we review essential microglial homeostatic functions regulated by SFKs, including phagocytosis, environmental sensing, and secretion of inflammatory mediators. In addition, we discuss the potential of SFK modulation for microglial homeostasis in Parkinson's and Alzheimer's diseases. Abstract : c‐Src was the first kinase described capable of phosphorylating tyrosine residues. Subsequent identification of other tyrosine‐phosphorylating protein kinases with a similar structure to c‐Src gave rise to the Src family kinases (SFKs). These kinases are expressed on microglia. Here, we review essential microglial homeostatic functions regulated by SFKs, including phagocytosis, environmental sensing, secretion of inflammatory mediators, and the potential of SFK modulation for microglial homeostasis in Parkinson's and Alzheimer's diseases.