PubMed: 29255009

FK506-Binding Protein 12.6/1b, a Negative Regulator of [Ca<sup>2+</sup>], Rescues Memory and Restores Genomic Regulation in the Hippocampus of Aging Rats.
The Journal of neuroscience : the official journal of the Society for Neuroscience
Blalock EM | Chen KC | Gant JC | Kadish I | Landfield PW | Porter NM | Thibault O

Evidence 2c9a59bba7

Genes in the mTOR pathway were also of specific interest because this pathway is inhibited by the immunosuppressant drug rapamy- cin via complex formation with FKBP1b/1a.

Evidence 0fb964ef9d

Nevertheless, the lack of change in mTOR pathway gene expression suggests that FKBP1b’s genomic effects were not mediated by the mTOR pathway.

Evidence 524447e694

MAP2: downregulation with aging and restoration by FKBP1b

Evidence 8706951f13

Cpn-1 (calpain-1) and Ppp3cc (calcineurin, Nixon et al., 1994; Rozkalne et al., 2011; Furman and Norris, 2014), as well as a Ca2􏰅 release-activated Ca2􏰅 channel (ORAI1) were altered by aging and restored by FKBP1b treatment (Table 3).

Evidence 71a0168cf9

Moreover, FKBP1a, a close isoform of FKBP1b, negatively regulates mTOR in the brain, even in the absence of rapamycin

Evidence 31faed58fe

FKBP1b overexpression improved spatial reference and reversal memory for both LT and ST aged groups

Evidence 0d0eccf1ea

Remarkably, only four of the 876 aging-dependent and FKBP1b- sensitive genes (Eif3g, Pla2g7, S100􏰌, and Snapc2) exhibited exac- erbation of aging effects by FKBP1b, whereas the other 872 changed in opposite directions with aging and FKBP1b treatment.

Evidence eddf9f5a8c

Genes downregulated with aging and upregulated by FKBP1b (AC downregulated vs YC, FKBP1b upregulated vs AC, template II) strongly overrepresented GO categories related to intracellular and extracellular structure, including: cytoskeleton, extracellular region passive transmembrane transporter activity, ectoderm devel- opment, regulation of actin cytoskeleton organization, and regulation of MAP kinase activity (Table 1)

Evidence 8b9da7be1f

Genes upregulated with aging and downregulated by FKBP1b (AC upregulated vs YC, FKBP1b downregulated vs AC, template IV) overrepresented GO category annotations related to extracel- lular remodeling and transporter activity, including extracellular matrix, primary transmembrane transporter activity, blood vessel development, regulation of cell motion, and membrane-bounded vesicle (Table 1)

Evidence b800976a3a

Because FKBP1b is a negative regulator of hippocampal neuronal Ca2􏰅 transients

Evidence 7aea05ea2c

Twenty-four mTOR pathway genes were identified by searching the GO data- base and the literature (Johnson et al., 2013). Of these 24, only two, Hif1an and Nfkb1, were significantly altered with both age (upregulated) and FKBP1b (downregulated), showing that the mTOR pathway was not statistically overrepresented by FKBP1b- sensitive genes (n.s., p 􏰆 0.78, binomial test).

Evidence 7300d44525

AAV-FKBP1b injection increased hippocampal FKBP1b protein and gene expression, particularly in the LT group


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