Src family kinases (SFKs): critical regulators of microglial homeostatic functions and neurodegeneration in Parkinson's and Alzheimer's diseases.
Camila Cabral PortugalTiago O AlmeidaRenato SocodatoJoão B RelvasPublished in: The FEBS journal (2021)
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.
Keyphrases
- inflammatory response
- neuropathic pain
- lipopolysaccharide induced
- lps induced
- tyrosine kinase
- gene expression
- cognitive decline
- immune response
- cerebral ischemia
- systematic review
- oxidative stress
- spinal cord
- protein kinase
- dna methylation
- patient safety
- transcription factor
- small molecule
- resting state
- risk assessment
- multiple sclerosis
- climate change
- protein protein
- functional connectivity
- rectal cancer