Krüppel-Like Factors Modulate Susceptibility To Neuropsychiatric Disorders

The Krüppel-like family (KLF) is an evolutionarily conserved family of zinc finger transcription factors, which bind to DNA sequences to modulate gene expression programs. KLFs modulate biological processes, including cell growth, differentiation, proliferation, and development. Selectively, KLF4, KLF6, KLF7, KLF9, and KLF10 coordinate the establishment and maturation of the central nervous system (CNS), modulating neurogenesis and neural differentiation. Also, KLFs modulate brain function by assisting blood-brain barrier (BBB) integrity and neuroinflammation. In fact, defective KLF2, KLF4, KLF6, KLF9, and KLF14 functions affect BBB integrity and enhance neuroinflammation, disrupting brain function. BBB integrity and neuroinflammation have been proposed as mutual contributors to neuropsychiatric disorders. Based on this context, in the current review, we will provide experimental evidence addressing molecular and cellular pathways activated by KLFs in neurodevelopment. We described the role of KLFs in BBB integrity as a cellular and molecular pathway favoring neuroinflammation in neuropsychiatric disorders. We focused our understanding on scientific evidence from preclinical models, and also, we integrated clinical data to enrich their contributions and mutual crosstalk.