Deletion of asparagine endopeptidase reduces anxiety- and depressive-like behaviors and improves abilities of spatial cognition in mice

Gao, Jing; Li, Kai; Du, Lingfang; Yin, Hongqiang; Tan, Xiaoyue; Yang, Zhuo

doi:10.1016/j.brainresbull.2018.07.010

Cited by 26 publications

(14 citation statements)

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“…No sample size calculations, but sample size was consistent with other studies in the field. 18,33 The time line of the experiment is shown in Figure 10. Intragastric Administration.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…In vivo electrophysiological recording was used to test the synaptic plasticity of mice in the PP to the DG region according to previously described methods. 33 First, mice were anesthetized with an intraperitoneal (i.p.) injection of urethane (dose of 1.2 g/kg, Sigma) and were fixed on the stereotaxic apparatus (Narishige, Japan), using an electric blanket to keep their body temperature constant.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

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Novel Multitarget Directed Tacrine Hybrids as Anti-Alzheimer’s Compounds Improved Synaptic Plasticity and Cognitive Impairment in APP/PS1 Transgenic Mice

Jiang

et al. 2020

ACS Chem. Neurosci.

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Alzheimer’s disease (AD) is a complex pathological neurodegenerative disease that seriously threatens human health. Therefore, how to effectively improve and treat AD is an urgent problem. In this study, a novel multitarget derivative based on tacrine (named 9i), which could work simultaneously on more than one pathological target, was used to treat AD model APP/PS1 transgenic mice. After 4 weeks of intragastric administration, cognitive function and synaptic plasticity were significantly improved and β-amyloid (Aβ) plaques that are main pathological hallmarks of AD were decreased in the APP/PS1 mice. On the one hand, 9i inhibited the excessive activation of the Raf/MEK/ERK signaling pathway to alleviate the loss of neurons, which provides a foundation for structural integrity. On the other hand, synaptic associated proteins and the density of synaptic spines were increased in APP/PS1 mice treated with 9i, which provides the basis for the improvement of synaptic plasticity and cognitive impairment. Interestingly, 9i also reduced Aβ plaques in the DG region, which is consistent with previous in vitro experiments showing that 9i inhibited the self-assembly of Aβ fibers, thus protecting neurons from Aβ plaque neurotoxicity. Our results suggest that 9i as a novel compound can effectively improve the cognitive function and the pathological changes of AD in APP/PS1 transgenic mice.

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“…No sample size calculations, but sample size was consistent with other studies in the field. 18,33 The time line of the experiment is shown in Figure 10. Intragastric Administration.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Section: ■ Materials and Methodsmentioning

confidence: 99%

Novel Multitarget Directed Tacrine Hybrids as Anti-Alzheimer’s Compounds Improved Synaptic Plasticity and Cognitive Impairment in APP/PS1 Transgenic Mice

Jiang

et al. 2020

ACS Chem. Neurosci.

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“…За результатами експериментальних досліджень встановлено, що дельта-секретаза, відома як ендопептидаза аспарагіну або легумаїн, -лізосомальна цистеїнова протеаза, що розщеплює і білок -прекурсор амілоїду (amyloid precursor protein -APP), і тау-білок, що опосередковують патологічні зміни при хворобі Альцгеймера [22,23]. Експресія і активність даного ферменту тісно пов'язані з багатьма патологічними процесами, у тому числі з атеросклерозом та запаленням [24], когнітивною дисфункцією при хворобі Альцгеймера [22, 23], а також при депресії та тривожності [24].…”

Section: рисунок 1 глутамін-глутаматний шлях в астроцитах та нейронаunclassified

Когнітивна Дисфункція В Дітей: Можливості Фармакологічної Корекції Із Застосуванням Комплексу Амінокислот Та Вітаміну В6

Кhaitovych¹

2021

INJ

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Когнітивна дисфункція в дітей: можливості фармакологічної корекції із застосуванням комплексу амінокислот та вітаміну В 6 Резюме. До когнітивних функцій належить здатність розуміти, пізнавати, вивчати, усвідомлювати, сприймати і переробляти зовнішню інформацію. Серед основних причин виникнення когнітивної дисфункції виділяють перинатальне ушкодження центральної нервової системи або асфіксію, екологічні фактори. При когнітивній дисфункції в дітей спостерігаються порушення розвитку навчальних навичок, моторних функцій, змішані специфічні розлади розвитку. Найчастіша скарга -зниження концентрації уваги відмічається у 21 % дітей України. Когнітивна дисфункція часто поєднується з депресією, тривожністю, адитивною поведінкою; практично в половини пацієнтів переходить у дорослий вік. Серед механізмів розвитку когнітивної дисфункції ключову роль відіграють оксидативний стрес та низькоінтенсивне запалення в нейронах. За результатами експериментальних та клінічних досліджень доведено, що компоненти комплексного препарату Когівіс амінокислоти аспарагін і глутамін, а також DL-фосфосерин і вітамін В 6 сприяють розвитку мозку; забезпечують синтез білків, нуклеотидів, нейротрансмітерів, глутатіону тощо; впливають на оксидативний стрес у центральній нервовій системі, зокрема в гіпокампі. Все це створює умови для оптимального функціонування нейронів і розвитку когнітивних функцій.

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“…In mouse experiments, general symptoms of emotional problems such as anxiety and depression were reduced after the deletion of AEP knockout. In addition, spatial cognition and learning ability were also improved in AEP knockout mice compared with wild-type mice [ 80 ].…”

Section: Enzymes Related To Ad and Pdmentioning

confidence: 99%

Target Enzymes Considered for the Treatment of Alzheimer’s Disease and Parkinson’s Disease

Kim

Lee

2020

BioMed Research International

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Various amyloidogenic proteins have been suggested to be involved in the onset and progression of neurodegenerative diseases (ND) such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Particularly, the aggregation of misfolded amyloid-β and hyperphosphorylated tau and α-synuclein are linked to the pathogenesis of AD and PD, respectively. In order to care the diseases, multiple small molecules have been developed to regulate the aggregation pathways of these amyloid proteins. In addition to controlling the aggregation of amyloidogenic proteins, maintaining the levels of the proteins in the brain by amyloid degrading enzymes (ADE; neprilysin (NEP), insulin-degrading enzyme (IDE), asparagine endopeptidase (AEP), and ADAM10) is also essential to cure AD and PD. Therefore, numerous biological molecules and chemical agents have been investigated as either inducer or inhibitor against the levels and activities of ADE. Although the side effect of enhancing the activity of ADE could occur, the removal of amyloidogenic proteins could result in a relatively good strategy to treat AD and PD. Furthermore, since the causes of ND are diverse, various multifunctional (multitarget) chemical agents have been designed to control the actions of multiple risk factors of ND, including amyloidogenic proteins, metal ions, and reactive oxygen species. Many of them, however, were invented without considerations of regulating ADE levels and actions. Incorporation of previously created molecules with the chemical agents handling ADE could be a promising way to treat AD and PD. This review introduces the ADE and molecules capable of modulating the activity and expression of ADE.

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Deletion of asparagine endopeptidase reduces anxiety- and depressive-like behaviors and improves abilities of spatial cognition in mice

Cited by 26 publications

References 57 publications

Novel Multitarget Directed Tacrine Hybrids as Anti-Alzheimer’s Compounds Improved Synaptic Plasticity and Cognitive Impairment in APP/PS1 Transgenic Mice

Novel Multitarget Directed Tacrine Hybrids as Anti-Alzheimer’s Compounds Improved Synaptic Plasticity and Cognitive Impairment in APP/PS1 Transgenic Mice

Когнітивна Дисфункція В Дітей: Можливості Фармакологічної Корекції Із Застосуванням Комплексу Амінокислот Та Вітаміну В6

Target Enzymes Considered for the Treatment of Alzheimer’s Disease and Parkinson’s Disease

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