TY - JOUR
T1 - Neuroinflammation and the Kynurenine pathway in CNS disease
T2 - Molecular mechanisms and therapeutic implications
AU - Mithaiwala, Mustafa N.
AU - Santana-Coelho, Danielle
AU - Porter, Grace A.
AU - O’connor, Jason C.
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/6
Y1 - 2021/6
N2 - Diseases of the central nervous system (CNS) remain a significant health, social and eco-nomic problem around the globe. The development of therapeutic strategies for CNS conditions has suffered due to a poor understanding of the underlying pathologies that manifest them. Understanding common etiological origins at the cellular and molecular level is essential to enhance the development of efficacious and targeted treatment options. Over the years, neuroinflammation has been posited as a common link between multiple neurological, neurodegenerative and neuropsy-chiatric disorders. Processes that precipitate neuroinflammatory conditions including genetics, in-fections, physical injury and psychosocial factors, like stress and trauma, closely link dysregulation in kynurenine pathway (KP) of tryptophan metabolism as a possible pathophysiological factor that ‘fuel the fire’ in CNS diseases. In this study, we aim to review emerging evidence that provide mechanistic insights between different CNS disorders, neuroinflammation and the KP. We provide a thorough overview of the different branches of the KP pertinent to CNS disease pathology that have therapeutic implications for the development of selected and efficacious treatment strategies.
AB - Diseases of the central nervous system (CNS) remain a significant health, social and eco-nomic problem around the globe. The development of therapeutic strategies for CNS conditions has suffered due to a poor understanding of the underlying pathologies that manifest them. Understanding common etiological origins at the cellular and molecular level is essential to enhance the development of efficacious and targeted treatment options. Over the years, neuroinflammation has been posited as a common link between multiple neurological, neurodegenerative and neuropsy-chiatric disorders. Processes that precipitate neuroinflammatory conditions including genetics, in-fections, physical injury and psychosocial factors, like stress and trauma, closely link dysregulation in kynurenine pathway (KP) of tryptophan metabolism as a possible pathophysiological factor that ‘fuel the fire’ in CNS diseases. In this study, we aim to review emerging evidence that provide mechanistic insights between different CNS disorders, neuroinflammation and the KP. We provide a thorough overview of the different branches of the KP pertinent to CNS disease pathology that have therapeutic implications for the development of selected and efficacious treatment strategies.
KW - Affective disorders
KW - Depression
KW - Kynurenine pathway
KW - Microglia
KW - Neurodegeneration
KW - Neuroinflammation
KW - Therapeutic strategies
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U2 - 10.3390/cells10061548
DO - 10.3390/cells10061548
M3 - Review article
C2 - 34205235
AN - SCOPUS:85110363186
SN - 2073-4409
VL - 10
JO - Cells
JF - Cells
IS - 6
M1 - 1548
ER -