TY - JOUR
T1 - TAM receptor pathways at the crossroads of neuroinflammation and neurodegeneration
AU - Tondo, Giacomo
AU - Perani, Daniela
AU - Comi, Cristoforo
N1 - Publisher Copyright:
© 2019 Giacomo Tondo et al.
PY - 2019
Y1 - 2019
N2 - Increasing evidence suggests that pathogenic mechanisms underlying neurodegeneration are strongly linked with neuroinflammatory responses. Tyro3, Axl, and Mertk (TAM receptors) constitute a subgroup of the receptor tyrosine kinase family, cell surface receptors which transmit signals from the extracellular space to the cytoplasm and nucleus. TAM receptors and the corresponding ligands, Growth Arrest Specific 6 and Protein S, are expressed in different tissues, including the nervous system, playing complex roles in tissue repair, inflammation and cell survival, proliferation, and migration. In the nervous system, TAM receptor signalling modulates neurogenesis and neuronal migration, synaptic plasticity, microglial activation, phagocytosis, myelination, and peripheral nerve repair, resulting in potential interest in neuroinflammatory and neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Multiple Sclerosis. In Alzheimer and Parkinson diseases, a role of TAM receptors in neuronal survival and pathological protein aggregate clearance has been suggested, while in Multiple Sclerosis TAM receptors are involved in myelination and demyelination processes. To better clarify roles and pathways involving TAM receptors may have important therapeutic implications, given the fine modulation of multiple molecular processes which could be reached. In this review, we summarise the roles of TAM receptors in the central nervous system, focusing on the regulation of immune responses and microglial activities and analysing in vitro and in vivo studies regarding TAM signalling involvement in neurodegeneration.
AB - Increasing evidence suggests that pathogenic mechanisms underlying neurodegeneration are strongly linked with neuroinflammatory responses. Tyro3, Axl, and Mertk (TAM receptors) constitute a subgroup of the receptor tyrosine kinase family, cell surface receptors which transmit signals from the extracellular space to the cytoplasm and nucleus. TAM receptors and the corresponding ligands, Growth Arrest Specific 6 and Protein S, are expressed in different tissues, including the nervous system, playing complex roles in tissue repair, inflammation and cell survival, proliferation, and migration. In the nervous system, TAM receptor signalling modulates neurogenesis and neuronal migration, synaptic plasticity, microglial activation, phagocytosis, myelination, and peripheral nerve repair, resulting in potential interest in neuroinflammatory and neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Multiple Sclerosis. In Alzheimer and Parkinson diseases, a role of TAM receptors in neuronal survival and pathological protein aggregate clearance has been suggested, while in Multiple Sclerosis TAM receptors are involved in myelination and demyelination processes. To better clarify roles and pathways involving TAM receptors may have important therapeutic implications, given the fine modulation of multiple molecular processes which could be reached. In this review, we summarise the roles of TAM receptors in the central nervous system, focusing on the regulation of immune responses and microglial activities and analysing in vitro and in vivo studies regarding TAM signalling involvement in neurodegeneration.
UR - http://www.scopus.com/inward/record.url?scp=85072964474&partnerID=8YFLogxK
U2 - 10.1155/2019/2387614
DO - 10.1155/2019/2387614
M3 - Review article
SN - 0278-0240
VL - 2019
JO - Disease Markers
JF - Disease Markers
M1 - 2387614
ER -