Table 1.
The expressions and prospects of the FGF/FGFR system in cognitive disorders and dementia.
| Members | Receptors | Sample | Trends | Main effects | Prospects | References |
|---|---|---|---|---|---|---|
| FGF-1 | FGFR-1b,1c | Cortex homogenate (AD) | ↑ | Reduced inflammation and oxidative stress, repaired BBB, suppressed excitotoxicity, improved insulin sensitivity | AD, VaD, MCI, VCI | Takami et al. (1998), Thorns et al. (2001), Yamagata et al. (2004), Mashayekhi et al. (2010), Tsai et al. (2015), Wu et al. (2017), and Liang et al. (2021) |
| FGFR-2b,2c | Serum (AD) | ↓ | ||||
| FGFR-3b,3c | CSF (AD) | ↓ | ||||
| FGFR-4 | ||||||
| FGF-2 | FGFR-1b,1c | Cortex homogenate (AD) | ↑ | Promoted neurogenesis, inhibited neurotoxicity, extended neurons life-span, induced angiogenesis, inhibited inflammation | AD, VaD, HD | Jin et al. (2005), Duff et al. (2010), Wang et al. (2016), Tyebji and Hannan (2017), Liu M. et al. (2018), and Ilieva et al. (2019) |
| FGFR-2c | ||||||
| FGFR-3c | Serum (AD) | ↓ | ||||
| FGFR-4 | ||||||
| FGF-9 | FGFR-2c | Hippocampus homogenate (AD) | ↑ | Promoted neuronal development, inhibited oxidative stress, suppressed apoptosis, promoted neurogenesis | AD, HD | Nakamura et al. (1998), Chuang et al. (2015), and Yusuf et al. (2019, 2021a,b) |
| FGFR-3b,3c | Serum (HD) | ↓ | ||||
| FGF-17 | β-KL/FGFR-2 | N/A | N/A | Supported oligodendrocyte precursor cell growth, inhibited FGF-19 pathway | MCI | Liu S. et al. (2018) and Iram et al. (2022) |
| FGFR-3c | ||||||
| FGF-15/19 | β-KL/FGFR-4 | N/A | N/A | Inhibited HPA axis hyperexcitability, reduced insulin resistance, regulated neurotransmitter homeostasis, promoted neurogenesis, regulated bile acid metabolism | AD, MCI | Marcelin et al. (2014), McMillin et al. (2015), Perry et al. (2015), Mertens et al. (2017), Liu S. et al. (2018), and Li et al. (2020) |
| FGF-21 | β-KL/FGFR-1 | Serum (AD) | ↓ | Improved BBB integrity, repair cerebrovascular endothelium, inhibited inflammation, promoted neurogenesis, suppressed apoptosis, maintained neurotransmitter homeostasis, regulated lipid metabolism and glucose metabolism, enhanced insulin sensitivity | AD, VaD | Sa-Nguanmoo et al. (2016), Kuroda et al. (2017), Chen et al. (2018), Zheng et al. (2019), Jiang et al. (2020), and Wang et al. (2020) |
| PPAR-γ | ||||||
| FGF-23 | α-KL/FGFR-1c | Serum (MCI) | ↑ | Regulated phosphate homeostasis and glucose metabolism, promoted neurogenesis | MCI | Liu et al. (2011), Drew et al. (2014), and Drew and Weiner (2014) |
| FGFR-2c | ||||||
| FGFR-3c |
AD, Alzheimer’s disease; BBB, blood–brain barrier; CSF, cerebrospinal fluid; FGF, fibroblast growth factor; FGFR, fibroblast growth factor receptor; HD, Huntington’s dementia; MCI, mild cognitive impairment; VCI, vascular cognitive impairment; VaD, vascular dementia; α/β-KL, α/β-klotho protein.