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@ARTICLE{Biella:138753,
author = {Biella, Gloria and Fusco, Federica and Nardo, Emanuele and
Bernocchi, Ottavia and Colombo, Alessio and Lichtenthaler,
Stefan F and Forloni, Gianluigi and Albani, Diego},
title = {{S}irtuin 2 {I}nhibition {I}mproves {C}ognitive
{P}erformance and {A}cts on {A}myloid-β {P}rotein
{P}recursor {P}rocessing in {T}wo {A}lzheimer's {D}isease
{M}ouse {M}odels.},
journal = {Journal of Alzheimer's disease},
volume = {53},
number = {3},
issn = {1387-2877},
address = {Amsterdam},
publisher = {IOS Press},
reportid = {DZNE-2020-05075},
pages = {1193-1207},
year = {2016},
abstract = {The neuropathological hallmarks of Alzheimer's disease (AD)
are extracellular plaques built up by the accumulation of
the amyloid-β protein precursor (AβPP)-derived peptide β
(Aβ), and intracellular tangles of hyperphosphorylated tau
protein. Sirtuin 2 (SIRT2) is a member of the sirtuin
family, featuring conserved enzymes with deacetylase
activity and involved in several cell molecular pathways. We
investigated the importance of SIRT2 inhibition in AD. We
inhibited SIRT2 by small molecules (AGK-2, AK-7) and
examined AβPP metabolism in H4-SW neuroglioma cells
overexpressing AβPP and two AD transgenic mouse models
(3xTg-AD and APP23). The in vitro studies suggested that the
inhibition of SIRT2 reduced Aβ production; in vivo data
showed an improvement of cognitive performance in the novel
object recognition test, and an effect on AβPP proteolytic
processing leading to a reduction of soluble β-AβPP and an
increase of soluble α-AβPP protein. In 3xTg-AD mice, we
noticed that total tau protein level rose. Overall, our
pre-clinical data support a role for SIRT2 inhibition in the
improvement of cognitive performance and the modulation of
molecular mechanisms relevant for AD, thus deserving
attention as possible therapeutic strategy.},
keywords = {Alzheimer Disease: complications / Alzheimer Disease:
genetics / Alzheimer Disease: pathology / Amyloid
beta-Peptides: metabolism / Amyloid beta-Protein Precursor:
genetics / Amyloid beta-Protein Precursor: metabolism /
Animals / Benzamides: pharmacology / Benzamides: therapeutic
use / Brain: drug effects / Brain: metabolism /
Calcium-Binding Proteins: metabolism / Cell Line, Tumor /
Cognition Disorders: drug therapy / Cognition Disorders:
etiology / Cognition Disorders: metabolism / Cognition
Disorders: pathology / Disease Models, Animal / Enzyme
Inhibitors: pharmacology / Enzyme Inhibitors: therapeutic
use / Furans: pharmacology / Furans: therapeutic use / Gene
Expression Regulation: drug effects / Gene Expression
Regulation: genetics / Glial Fibrillary Acidic Protein:
metabolism / Glioma: pathology / Mice / Mice, Inbred C57BL /
Mice, Transgenic / Microfilament Proteins: metabolism /
Peptide Fragments: metabolism / Phosphorylation: drug
effects / Quinolines: pharmacology / Quinolines: therapeutic
use / Sirtuin 2: metabolism / Sulfonamides: pharmacology /
Sulfonamides: therapeutic use /
3-(1-azepanylsulfonyl)-N-(3-bromphenyl)benzamide (NLM
Chemicals) / AGK2 compound (NLM Chemicals) / Aif1 protein,
mouse (NLM Chemicals) / Amyloid beta-Peptides (NLM
Chemicals) / Amyloid beta-Protein Precursor (NLM Chemicals)
/ Benzamides (NLM Chemicals) / Calcium-Binding Proteins (NLM
Chemicals) / Enzyme Inhibitors (NLM Chemicals) / Furans (NLM
Chemicals) / Glial Fibrillary Acidic Protein (NLM Chemicals)
/ Microfilament Proteins (NLM Chemicals) / Peptide Fragments
(NLM Chemicals) / Quinolines (NLM Chemicals) / Sulfonamides
(NLM Chemicals) / amyloid beta-protein (1-40) (NLM
Chemicals) / amyloid beta-protein (1-42) (NLM Chemicals) /
Sirtuin 2 (NLM Chemicals)},
cin = {AG Lichtenthaler},
ddc = {610},
cid = {I:(DE-2719)1110006},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27372638},
doi = {10.3233/JAD-151135},
url = {https://pub.dzne.de/record/138753},
}