Implications of Krüppel-like factor signaling in neuroinflammation for neurodegenerative diseases

Abstract

Neurodegenerative diseases (NDs) pose a formidable challenge in modern healthcare and are characterized by progressive neuronal dysfunction and loss. Emerging research underscores the intricate interplay between neuroinflammation and mechanisms underlying ND pathogenesis. This review delves into the complex role of Krüppel-like factors (KLFs) in the context of neuroinflammation and major NDs. KLFs exert diverse effects in the brain on cellular processes such as blood-brain barrier integrity, neuronal cell cycle progression, and glial cell activation. Modulation of KLF expression and signaling emerges as a promising strategy to mitigate ND progression. By elucidating KLFs' multifaceted implications across diverse pathways and cellular processes implicated in ND progression, this review offers valuable insights into their therapeutic potential as targets for NDs.

Keywords: Krüppel-like factor; neurodegenerative disease; neuroinflammation.

Figure 1

KLFs play a role in blood-brain barrier integrity by modulating the expression of several tight junction proteins, enhancing mitochondrial function, and reducing apoptosis and oxidative stress (The arrow indicates activation, while the straight line with a “T-shape” end indicates inhibition. KLFs boxed in green indicate a neuroprotective effect. These labels apply to all the Figures that follow).

Figure 2

KLFs modulate neuroinflammation through glial polarization and ferroptosis by regulating various signaling pathways such as NF-κB, iron and JAK-STAT pathway.

Figure 3

KLFs regulate cell cycle progression in neuronal and glial cells.

Figure 4

KLFs modulate inflammasome and mitochondrial oxidation in glial cells, and mitophagy/autophagy in neurons.