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001-es BibID:BIBFORM019979
Első szerző:Engmann, Olivia
Cím:Schizophrenia is associated with dysregulation of a Cdk5 activator that regulates synaptic protein expression and cognition / Olivia Engmann, Tibor Hortobágyi, Ruth Pidsley, Claire Troakes, Hans-Gert Bernstein, Michael R. Kreutz, Jonathan Mill, Margareta Nikolic, Karl Peter Giese
Dátum:2011
ISSN:0006-8950
Megjegyzések:Cyclin-dependent kinase 5 is activated by small subunits, of which p35 is the most abundant. The functions of cyclin-dependent kinase 5 signalling in cognition and cognitive disorders remains unclear. Here, we show that in schizophrenia, a disorder associated with impaired cognition, p35 expression is reduced in relevant brain regions. Additionally, the expression of septin 7 and OPA1, proteins downstream of truncated p35, is decreased in schizophrenia. Mimicking a reduction of p35 in heterozygous knockout mice is associated with cognitive endophenotypes. Furthermore, a reduction of p35 in mice results in protein changes similar to schizophrenia post-mortem brain. Hence, heterozygous p35 knockout mice model both cognitive endophenotypes and molecular changes reminiscent of schizophrenia. These changes correlate with reduced acetylation of the histone deacetylase 1 target site H3K18 in mice. This site has previously been shown to be affected by truncated p35. By restoring H3K18 acetylation with the clinically used specific histone deacetylase 1 inhibitor MS-275 both cognitive and molecular endophenotypes of schizophrenia can be rescued in p35 heterozygous knockout mice. In summary, we suggest that reduced p35 expression in schizophrenia has an impact on synaptic protein expression and cognition and that these deficits can be rescued, at least in part, by the inhibition of histone deacetylase 1.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Brain. - 134 : 8 (2011), p. 2408-2421. -
További szerzők:Hortobágyi Tibor (1965-) (patológus) Pidsley, Ruth Troakes, Claire Bernstein, Hans-Gert Kreutz, Michael R. Mill, Jonathan Nikolic, Margareta Giese, Karl Peter
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001-es BibID:BIBFORM019968
Első szerző:Engmann, Olivia
Cím:Cyclin-dependent kinase 5 activator p25 is generated during memory formation and is reduced at an early stage in Alzheimer's disease / Olivia Engmann, Tibor Hortobágyi, Andrew J. Thompson, Jennifer Guadagno, Claire Troakes, Salvador Soriano, Safa Al-Sarraj, Yong Kim, Karl Peter Giese
Dátum:2011
ISSN:0006-3223
Megjegyzések:BACKGROUND: The cyclin-dependent kinase 5 activator p35 can be cleaved into p25. Formation of p25 has been suggested to contribute to neurodegeneration in Alzheimer's disease (AD). However, overexpression of low levels of p25 in mice enhances memory formation. Therefore, it has been suggested that p25 formation might be an event early in AD to compensate for impairments in synaptic plasticity. Ongoing p25 formation has been hypothesized to contribute to neurodegeneration at the later stages of AD. METHODS: Here, we tested the early compensation hypothesis by analyzing the levels of p25 and its precursor p35 in AD postmortem samples from different brain regions at different stages of tau pathology, using quantitative Western blots. Furthermore, we studied p35 and p25 during spatial memory formation. By employing quantitative mass spectrometry, we identified proteins downstream of p25, which were then studied in AD samples. RESULTS: We found that p25 is generated during spatial memory formation. Furthermore, we demonstrate that overexpression of p25 in the physiological range increases the expression of two proteins implicated in spine formation, septin 7 and optic atrophy 1. We show that the expression of p35 and p25 is reduced as an early event in AD. Moreover, expression of the p25-regulated protein optic atrophy 1 was reduced in a time course similar to p25 expression. CONCLUSIONS: Our findings suggest that p25 generation is a mechanism underlying hippocampal memory formation that is impaired in the early stages of AD. Our findings argue against the previously raised early compensation hypothesis and they propose that p25-mediated neurotoxicity does not occur in AD.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Biological Psychiatry. - 70 : 2 (2011), p. 159-168. -
További szerzők:Hortobágyi Tibor (1965-) (patológus) Thompson, Andrew J. Guadagno, Jennifer Troakes, Claire Soriano, Salvador Al-Sarraj, Safa Kim, Yong Giese, Karl Peter
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3.

001-es BibID:BIBFORM104873
035-os BibID:(cikkazonosító)fcac192 (scopus)85135692025 (wos)000835001700004
Első szerző:Rupawala, Huzefa
Cím:Cysteine string protein alpha accumulates with early pre-synaptic dysfunction in Alzheimer's disease / Rupawala Huzefa, Shah Keshvi, Davies Caitlin, Rose Jamie, Colom-Cadena Marti, Peng Xianhui, Granat Lucy, Aljuhani Manal, Mizuno Keiko, Troakes Claire, Perez-Nievas Beatriz Gomez, Morgan Alan, So Po-Wah, Hortobagyi Tibor, Spires-Jones Tara L., Noble Wendy, Giese Karl Peter
Dátum:2022
ISSN:2632-1297
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Brain Communications. - 4 (2022), p. 1-15. -
További szerzők:Shah, Keshvi Davies, Caitlin Rose, Jamie Colom-Cadena, Marti Peng, Xianhui Granat, Lucy Aljuhani, Manal Mizuno, Keiko Troakes, Claire Perez-Nievas, Beatriz Gomez Morgan, Alan So, Po-Wah Hortobágyi Tibor (1965-) (patológus) Spires-Jones, Tara L. Noble, Wendy Giese, Karl Peter
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4.

001-es BibID:BIBFORM065658
Első szerző:Tiwari, Sachin Suresh
Cím:Alzheimer-related decrease in CYFIP2 links amyloid production to tau hyperphosphorylation and memory loss / Sachin Suresh Tiwari, Keiko Mizuno, Anshua Ghosh, Wajeeha Aziz, Claire Troakes, Jason Daoud, Vidushi Golash, Wendy Noble, Tibor Hortobágyi, Karl Peter Giese
Dátum:2016
ISSN:0006-8950
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Brain 139 : Pt10 (2016), p. 2751-2765. -
További szerzők:Mizuno, Keiko Ghosh, Anshua Aziz, Wajeeha Troakes, Claire Daoud, Jason Golash, Vidushi Noble, Wendy Hortobágyi Tibor (1965-) (patológus) Giese, Karl Peter
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5.

001-es BibID:BIBFORM063338
Első szerző:Tiwari, Sachin Suresh
Cím:Evidence that the presynaptic vesicle protein CSPalpha is a key player in synaptic degeneration and protection in Alzheimer's disease / Sachin S. Tiwari, Marie d'Orange, Claire Troakes, Badrun N. Shurovi, Olivia Engmann, Wendy Noble, Tibor Hortobágyi, Karl P. Giese
Dátum:2015
ISSN:1756-6606
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Molecular Brain. - 8 : 1 (2015), p. 1-12. -
További szerzők:d'Orange, Marie Troakes, Claire Shurovi, Badrun N. Engmann, Olivia Noble, Wendy Hortobágyi Tibor (1965-) (patológus) Giese, Karl Peter
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