FSH blockade improves cognition in mice with Alzheimer’s disease


  • Sowers, M. et al. Modifications in physique composition in ladies over six years at midlife: ovarian and chronological growing old. J. Clin. Endocrinol. Metab. 92, 895–901 (2007).

    CAS 
    PubMed 

    Google Scholar 

  • Sowers, M. R. et al. Hormone predictors of bone mineral density modifications throughout the menopausal transition. J. Clin. Endocrinol. Metab. 91, 1261–1267 (2006).

    CAS 
    PubMed 

    Google Scholar 

  • Guo, Y. et al. Blocking FSH inhibits hepatic ldl cholesterol biosynthesis and reduces serum ldl cholesterol. Cell Res. 29, 151–166 (2019).

    CAS 
    PubMed 

    Google Scholar 

  • Han, X. et al. A novel follicle-stimulating hormone vaccine for controlling fats accumulation. Theriogenology 148, 103–111 (2020).

    CAS 
    PubMed 

    Google Scholar 

  • Ji, Y. et al. Epitope-specific monoclonal antibodies to FSHβ enhance bone mass. Proc. Natl Acad. Sci. USA 115, 2192–2197 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Liu, P. et al. Blocking FSH induces thermogenic adipose tissue and reduces physique fats. Nature 546, 107–112 (2017).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Geng, W. et al. Immunization with FSHβ fusion protein antigen prevents bone loss in a rat ovariectomy-induced osteoporosis mannequin. Biochem. Biophys. Res. Commun. 434, 280–286 (2013).

    CAS 
    PubMed 

    Google Scholar 

  • Fisher, D. W., Bennett, D. A. & Dong, H. Sexual dimorphism in predisposition to Alzheimer’s illness. Neurobiol. Getting old 70, 308–324 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Andersen, Ok. et al. Gender variations within the incidence of AD and vascular dementia: the EURODEM research. EURODEM Incidence Analysis Group. Neurology 53, 1992–1997 (1999).

    CAS 
    PubMed 

    Google Scholar 

  • Marongiu, R. Accelerated ovarian failure as a singular mannequin to check peri-menopause affect on Alzheimer’s illness. Entrance. Getting old Neurosci. 11, 242 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Matyi, J. M., Rattinger, G. B., Schwartz, S., Buhusi, M. & Tschanz, J. T. Lifetime estrogen publicity and cognition in late life: the Cache County examine. Menopause 26, 1366–1374 (2019).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Zandi, P. P. et al. Hormone alternative remedy and incidence of Alzheimer illness in older ladies: the Cache County Examine. JAMA 288, 2123–2129 (2002).

    CAS 
    PubMed 

    Google Scholar 

  • O’Brien, J., Jackson, J. W., Grodstein, F., Blacker, D. & Weuve, J. Postmenopausal hormone remedy just isn’t related to danger of all-cause dementia and Alzheimer’s illness. Epidemiol. Rev. 36, 83–103 (2014).

    PubMed 

    Google Scholar 

  • Shumaker, S. A. et al. Conjugated equine estrogens and incidence of possible dementia and delicate cognitive impairment in postmenopausal ladies: Girls’s Well being Initiative Reminiscence Examine. JAMA 291, 2947–2958 (2004).

    CAS 
    PubMed 

    Google Scholar 

  • Brief, R. A., Bowen, R. L., O’Brien, P. C. & Graff-Radford, N. R. Elevated gonadotropin ranges in sufferers with Alzheimer illness. Mayo Clin. Proc. 76, 906–909 (2001).

    CAS 
    PubMed 

    Google Scholar 

  • Bowen, R. L., Isley, J. P. & Atkinson, R. L. An affiliation of elevated serum gonadotropin concentrations and Alzheimer illness? J. Neuroendocrinol. 12, 351–354 (2000).

    CAS 
    PubMed 

    Google Scholar 

  • Randolph, J. F. Jr et al. Change in follicle-stimulating hormone and estradiol throughout the menopausal transition: impact of age on the last menstrual interval. J. Clin. Endocrinol. Metab. 96, 746–754 (2011).

    CAS 
    PubMed 

    Google Scholar 

  • Epperson, C. N., Sammel, M. D. & Freeman, E. W. Menopause results on verbal reminiscence: findings from a longitudinal group cohort. J. Clin. Endocrinol. Metab. 98, 3829–3838 (2013).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Greendale, G. A. et al. Results of the menopause transition and hormone use on cognitive efficiency in midlife ladies. Neurology 72, 1850–1857 (2009).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Meyer, P. M. et al. A population-based longitudinal examine of cognitive functioning within the menopausal transition. Neurology 61, 801–806 (2003).

    CAS 
    PubMed 

    Google Scholar 

  • Zhu, L. L. et al. Blocking antibody to the β-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis. Proc. Natl Acad. Sci. USA 109, 14574–14579 (2012).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Oddo, S. et al. Triple-transgenic mannequin of Alzheimer’s illness with plaques and tangles: intracellular Aβ and synaptic dysfunction. Neuron 39, 409–421 (2003).

    CAS 
    PubMed 

    Google Scholar 

  • Webster, S. J., Bachstetter, A. D., Nelson, P. T., Schmitt, F. A. & Van Eldik, L. J. Utilizing mice to mannequin Alzheimer’s dementia: an outline of the medical illness and the preclinical behavioral modifications in 10 mouse fashions. Entrance. Genet. 5, 88 (2014).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Carroll, J. C. et al. Progesterone and estrogen regulate Alzheimer-like neuropathology in feminine 3xTg-AD mice. J. Neurosci. 27, 13357–13365 (2007).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhang, Z. et al. Cleavage of tau by asparagine endopeptidase mediates the neurofibrillary pathology in Alzheimer’s illness. Nat. Med. 20, 1254–1262 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhang, Z. et al. Delta-secretase cleaves amyloid precursor protein and regulates the pathogenesis in Alzheimer’s illness. Nat. Commun. 6, 8762 (2015).

    ADS 
    CAS 
    PubMed 

    Google Scholar 

  • Rocca, W. A. et al. Elevated danger of cognitive impairment or dementia in ladies who underwent oophorectomy earlier than menopause. Neurology 69, 1074–1083 (2007).

    CAS 
    PubMed 

    Google Scholar 

  • Tokuyama, N. et al. Particular person and mixing results of anti-RANKL monoclonal antibody and teriparatide in ovariectomized mice. Bone Rep. 2, 1–7 (2015).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Rosen, C. J. & Zaidi, M. Contemporaneous copy of preclinical science: a case examine of FSH and fats. Ann. N. Y. Acad. Sci. 1404, 17–19 (2017).

    ADS 
    PubMed 

    Google Scholar 

  • Minkeviciene, R. et al. Age-related lower in stimulated glutamate launch and vesicular glutamate transporters in APP/PS1 transgenic and wild-type mice. J. Neurochem. 105, 584–594 (2008).

    CAS 
    PubMed 

    Google Scholar 

  • Onos, Ok. D. et al. Enhancing face validity of mouse fashions of Alzheimer’s illness with pure genetic variation. PLoS Genet. 15, e1008155 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Volianskis, A., Kostner, R., Molgaard, M., Hass, S. & Jensen, M. S. Episodic reminiscence deficits usually are not associated to altered glutamatergic synaptic transmission and plasticity within the CA1 hippocampus of the APPswe/PS1deltaE9-deleted transgenic mice mannequin of ss-amyloidosis. Neurobiol. Getting old 31, 1173–1187 (2010).

    CAS 
    PubMed 

    Google Scholar 

  • Araujo, A. B. & Wittert, G. A. Endocrinology of the growing old male. Greatest Pract. Res. Clin. Endocrinol. Metab. 25, 303–319 (2011).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Casadesus, G. et al. Will increase in luteinizing hormone are related to declines in cognitive efficiency. Mol. Cell. Endocrinol. 269, 107–111 (2007).

    CAS 
    PubMed 

    Google Scholar 

  • Berry, A., Tomidokoro, Y., Ghiso, J. & Thornton, J. Human chorionic gonadotropin (a luteinizing hormone homologue) decreases spatial reminiscence and will increase mind amyloid-β ranges in feminine rats. Horm. Behav. 54, 143–152 (2008).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Liu, T., Wimalasena, J., Bowen, R. L. & Atwood, C. S. Luteinizing hormone receptor mediates neuronal pregnenolone manufacturing by way of up-regulation of steroidogenic acute regulatory protein expression. J. Neurochem. 100, 1329–1339 (2007).

    CAS 
    PubMed 

    Google Scholar 

  • Gera, S. et al. First-in-class humanized FSH blocking antibody targets bone and fats. Proc. Natl Acad. Sci. USA 117, 28971–28979 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Straccia, M. et al. Professional-inflammatory gene expression and neurotoxic results of activated microglia are attenuated by absence of CCAAT/enhancer binding protein β. J. Neuroinflammation 8, 156 (2011).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ramji, D. P. & Foka, P. CCAAT/enhancer-binding proteins: construction, operate and regulation. Biochem. J. 365, 561–575 (2002).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, Z. H. et al. Delta-secretase phosphorylation by SRPK2 enhances its enzymatic exercise, scary pathogenesis in Alzheimer’s illness. Mol. Cell 67, 812–825 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Solar, L. et al. FSH straight regulates bone mass. Cell 125, 247–260 (2006).

    CAS 
    PubMed 

    Google Scholar 

  • Hammond, S. L., Leek, A. N., Richman, E. H. & Tjalkens, R. B. Mobile selectivity of AAV serotypes for gene supply in neurons and astrocytes by neonatal intracerebroventricular injection. PLoS ONE 12, e0188830 (2017).

    PubMed 
    PubMed Central 

    Google Scholar 

  • von Jonquieres, G. et al. Recombinant human myelin-associated glycoprotein promoter drives selective AAV-mediated transgene expression in oligodendrocytes. Entrance. Mol. Neurosci. 9, 13 (2016).

    Google Scholar 

  • Randolph, J. F. Jr. et al. Reproductive hormones within the early menopausal transition: relationship to ethnicity, physique measurement, and menopausal standing. J. Clin. Endocrinol. Metab. 88, 1516–1522 (2003).

    CAS 
    PubMed 

    Google Scholar 

  • Ashe, Ok. H. & Zahs, Ok. R. Probing the biology of Alzheimer’s illness in mice. Neuron 66, 631–645 (2010).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Millward, C. A. et al. Mice with a deletion within the gene for CCAAT/enhancer-binding protein β are protected in opposition to diet-induced weight problems. Diabetes 56, 161–167 (2007).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zaidi, M. et al. Actions of pituitary hormones past conventional targets. J. Endocrinol. 237, R83–R98 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Silverman, E., Eimerl, S. & Orly, J. CCAAT enhancer-binding protein β and GATA-4 binding areas throughout the promoter of the steroidogenic acute regulatory protein (StAR) gene are required for transcription in rat ovarian cells. J. Biol. Chem. 274, 17987–17996 (1999).

    CAS 
    PubMed 

    Google Scholar 

  • Sirois, J. & Richards, J. S. Transcriptional regulation of the rat prostaglandin endoperoxide synthase 2 gene in granulosa cells. Proof for the position of a cis-acting C/EBPβ promoter component. J. Biol. Chem. 268, 21931–21938 (1993).

    CAS 
    PubMed 

    Google Scholar 

  • Wang, H., Liu, X., Chen, S. & Ye, Ok. Spatiotemporal activation of the C/EBPβ/δ-secretase axis regulates the pathogenesis of Alzheimer’s illness. Proc. Natl Acad. Sci. USA 115, E12427–E12434 (2018).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Sterneck, E., Tessarollo, L. & Johnson, P. F. A necessary position for C/EBPβ in feminine copy. Genes Dev. 11, 2153–2162 (1997).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Minkeviciene, R. et al. Amyloid β-induced neuronal hyperexcitability triggers progressive epilepsy. J. Neurosci. 29, 3453–3462 (2009).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhang, Z. et al. 7,8-dihydroxyflavone prevents synaptic loss and reminiscence deficits in a mouse mannequin of Alzheimer’s illness. Neuropsychopharmacology 39, 638–650 (2014).

    PubMed 

    Google Scholar 

  • Xiang, J. et al. Delta-secretase-cleaved Tau antagonizes TrkB neurotrophic signalings, mediating Alzheimer’s illness pathologies. Proc. Natl Acad. Sci. USA 116, 9094–9102 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Leger, M. et al. Object recognition take a look at in mice. Nat. Protoc. 8, 2531–2537 (2013).

    CAS 
    PubMed 

    Google Scholar 

  • Ioannidis, J. P. Why most printed analysis findings are false. PLoS Med. 2, e124 (2005).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Collins, F. S. & Tabak, L. A. Coverage: NIH plans to reinforce reproducibility. Nature 505, 612–613 (2014).

    ADS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • McNutt, M. Reproducibility. Science 343, 229 (2014).

    ADS 
    CAS 
    PubMed 

    Google Scholar 

  • Mullard, A. Most cancers reproducibility venture yields first outcomes. Nat. Rev. Drug Discov. 16, 77 (2017).

    PubMed 

    Google Scholar 

  • Horrigan, S. Ok. et al. Replication examine: melanoma genome sequencing reveals frequent PREX2 mutations. eLife 6, e21634 (2017).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Horrigan, S. Ok., Reproducibility Venture: Most cancers Biology. Replication examine: the CD47-signal regulatory protein alpha (SIRPa) interplay is a therapeutic goal for human stable tumors. eLife 6, e18173 (2017).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Leave a Reply