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MT5-MMP is a new pro-amyloidogenic proteinase that promotes amyloid pathology and cognitive decline in a transgenic mouse model of Alzheimer’s disease
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MT5-MMP can modulate neuronal activity.
“We and others previously reported that MT5-MMP can modulate neuronal activity [8, 9, 12, 13].”
Amyloid precursor protein (APP) is a relevant substrate of MT5-MMP.
“Amyloid precursor protein (APP) is another relevant substrate of MT5-MMP [11–13], which holds a central position in Alzheimer’s disease (AD) pathogenesis.”
This could contribute to the inability to detect steady-state C99 levels and thus mask a putative impact of MT5-MMP in C99 metabolism.
“Taken together, this could contribute to the inability to detect steady-state C99 levels and thus mask a putative impact of MT5-MMP in C99 metabolism, as previously shown in adult 5xFAD mice [13, 17].”
MT5-MMP deletion decreases IL-1β levels in the brains of 5xFAD mice at prodromal stages of the pathology.
“MT5-MMP deletion resulted in decreased IL-1β levels in the brains of 5xFAD mice at prodromal stages of the pathology, indicating functional interactions between IL-1β and MT5-MMP [13].”
MT5-MMP has the capacity to control Aβ levels.
“The above data denote the capacity of MT5-MMP to control Aβ levels, echoing our pioneer work in vivo [13]”
C99 did not accumulate in developing neural cells.
“C99 did not accumulate in developing neural cells.”
MT5-MMP deficiency in 5xFAD mice prevents glial reactivity and the increase in the levels of pro-inflammatory interleukin-1 beta (IL-1β).
“MT5-MMP deficiency also prevented glial reactivity and the increase in the levels of pro-inflammatory interleukin-1 beta (IL-1β) in 5xFAD mice [13].”
MT5-MMP cleavage of APP occurs in vivo in the brains of the 5xFAD mouse model of Alzheimer's disease.
“We found this cleavage to occur in vivo in the brains of the 5xFAD mouse model of AD [13].”
MT5-MMP deficiency prevents deficits in long-term potentiation (LTP), spatial learning and working memory in 5xFAD mice.
“concomitant with prevention of deficits in long-term potentiation (LTP), spatial learning and working memory [13, 17].”
MT5-MMP deficiency markedly reduces the levels of Aβ and C99 in early stages of Alzheimer's disease pathology.
“MT5-MMP is a new pro-amyloidogenic factor, whose deficiency markedly reduced the levels of Aβ and C99 in early stages of the pathology”
MT5-MMP can modulate APP/Aβ metabolism.
“Knowing that MT5-MMP can modulate APP/Aβ metabolism [13, 17]”
The impact of MT5-MMP in AD may begin at a stage well before the onset of obvious pathological and clinical signs.
“Such regulation highlights that the impact of MT5-MMP in AD, previously described in adult mice [13, 17], may actually begin at a stage well before the onset of obvious pathological and clinical signs.”
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RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
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“monitored by the 14D6 and 192swe antibodies, which are, respectively, considered as a readout of a- and b-secretase activities [2].”
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Metadata
- Authors
- Baranger, K., Marchalant, Y., Bonnet, A. E., Crouzin, N., Carrete, A., Paumier, J.-M., Py, N. A., Bernard, A., Bauer, C., Charrat, E., Moschke, K., Seiki, M., Vignes, M., Lichtenthaler, S. F., Checler, F., Khrestchatisky, M., & Rivera, S.
- Venue
- Cellular and Molecular Life Sciences
- Published
- 2015-07-23
- Volume
- 73
- Issue
- 1
- Pages
- 217-236
- ISSN
- 1420-682X
- 1420-9071
- PMC
- PMC4700096
- Cited by
- 133
- References
- 18
- Language
- en
- Funders
- Agence Nationale de la Recherche
- LECMA Vaincre l'Alzheimer
- Association France Alzheimer
- Fonds Européen de Développement Régional FEDER in PACA
- Bavarian-French University Center
- Deutsche Forschungsgemeinschaft
- Fondation pour la Recherche Médicale
- LABEX DISTALZ
- Marie Curie International Reintegration Grant
- Fondation Plan Alzheimer
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