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Literature DB >> 29602679

A new target for Alzheimer's disease: A small molecule SERCA activator is neuroprotective in vitro and improves memory and cognition in APP/PS1 mice.

Abstract

Amongst the cellular cacophony of altered signals in Alzheimer's disease (AD), disrupted Ca2+ homeostasis and consequential endoplasmic reticulum (ER) stress signals have been recognized as key determinants of neuron fate. This altered Ca2+ state is accompanied by a failing sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump, which has been recognized as a causal feature of the underlying disease state. Repair of the Ca2+ dyshomeostasis represents a putative drug target via alleviation of ER stress and rescue of injured neurons, effectively modifying the AD state. Herein, we report a small molecule SERCA activator that rescues brain cells and raises ER Ca2+ in vitro, and shows efficacy in the APP/PS1 double transgenic mouse model of Alzheimer's disease. These results support SERCA activation as a therapeutic target for AD.

Entities: Chemical Disease Gene Species

Keywords: Alzheimer’s disease; Drug discovery; ER stress; Medicinal chemistry; Neurodegeneration; SERCA; Small molecules

Mesh：

Substances：

Year: 2018 PMID： 29602679 DOI： 10.1016/j.bmcl.2018.03.052

Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823

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Cited

17 in total

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2. Chronic but not acute pharmacological activation of SERCA induces behavioral and neurochemical effects in male and female mice.

Authors: Aikaterini Britzolaki; Claire C Cronin; Patrick R Flaherty; Riely L Rufo; Pothitos M Pitychoutis
Journal: Behav Brain Res Date: 2020-11-01 Impact factor: 3.332

3. Pharmacological activation of SERCA ameliorates dystrophic phenotypes in dystrophin-deficient mdx mice.

Authors: Ken'ichiro Nogami; Yusuke Maruyama; Fusako Sakai-Takemura; Norio Motohashi; Ahmed Elhussieny; Michihiro Imamura; Satoshi Miyashita; Megumu Ogawa; Satoru Noguchi; Yuki Tamura; Jun-Ichi Kira; Yoshitsugu Aoki; Shin'ichi Takeda; Yuko Miyagoe-Suzuki
Journal: Hum Mol Genet Date: 2021-05-31 Impact factor: 6.150

Review 4. Advances in Multi-Functional Ligands and the Need for Metal-Related Pharmacology for the Management of Alzheimer Disease.

Authors: Abha Sharma; Vidhu Pachauri; S J S Flora
Journal: Front Pharmacol Date: 2018-11-15 Impact factor: 5.810

5. HEWL interacts with dissipated oleic acid micelles, and decreases oleic acid cytotoxicity.

Authors: Qin Huang; Dan Sun; Muhammad Zubair Hussain; Yonggang Liu; Ludmilla A Morozova-Roche; Ce Zhang
Journal: PLoS One Date: 2019-02-22 Impact factor: 3.240

6. Restoration of Sarcoplasmic Reticulum Ca²⁺ ATPase (SERCA) Activity Prevents Age-Related Muscle Atrophy and Weakness in Mice.

Authors: Rizwan Qaisar; Gavin Pharaoh; Shylesh Bhaskaran; Hongyang Xu; Rojina Ranjit; Jan Bian; Bumsoo Ahn; Constantin Georgescu; Jonathan D Wren; Holly Van Remmen
Journal: Int J Mol Sci Date: 2020-12-22 Impact factor: 6.208

A new target for Alzheimer's disease: A small molecule SERCA activator is neuroprotective in vitro and improves memory and cognition in APP/PS1 mice.

Review 1. Channels that Cooperate with TRPV4 in the Brain.

2. Chronic but not acute pharmacological activation of SERCA induces behavioral and neurochemical effects in male and female mice.

3. Pharmacological activation of SERCA ameliorates dystrophic phenotypes in dystrophin-deficient mdx mice.

Review 4. Advances in Multi-Functional Ligands and the Need for Metal-Related Pharmacology for the Management of Alzheimer Disease.

5. HEWL interacts with dissipated oleic acid micelles, and decreases oleic acid cytotoxicity.

6. Restoration of Sarcoplasmic Reticulum Ca²⁺ ATPase (SERCA) Activity Prevents Age-Related Muscle Atrophy and Weakness in Mice.

7. Restoration of SERCA ATPase prevents oxidative stress-related muscle atrophy and weakness.

Review 8. Axonal Endoplasmic Reticulum Dynamics and Its Roles in Neurodegeneration.

9. Putative autoantibodies in the cerebrospinal fluid of Alzheimer's disease patients.

Review 10. Ca²⁺ Dyshomeostasis Disrupts Neuronal and Synaptic Function in Alzheimer's Disease.

A new target for Alzheimer's disease: A small molecule SERCA activator is neuroprotective in vitro and improves memory and cognition in APP/PS1 mice.

Review 1. Channels that Cooperate with TRPV4 in the Brain.

2. Chronic but not acute pharmacological activation of SERCA induces behavioral and neurochemical effects in male and female mice.

3. Pharmacological activation of SERCA ameliorates dystrophic phenotypes in dystrophin-deficient mdx mice.

Review 4. Advances in Multi-Functional Ligands and the Need for Metal-Related Pharmacology for the Management of Alzheimer Disease.

5. HEWL interacts with dissipated oleic acid micelles, and decreases oleic acid cytotoxicity.

6. Restoration of Sarcoplasmic Reticulum Ca2+ ATPase (SERCA) Activity Prevents Age-Related Muscle Atrophy and Weakness in Mice.

7. Restoration of SERCA ATPase prevents oxidative stress-related muscle atrophy and weakness.

Review 8. Axonal Endoplasmic Reticulum Dynamics and Its Roles in Neurodegeneration.

9. Putative autoantibodies in the cerebrospinal fluid of Alzheimer's disease patients.

Review 10. Ca2+ Dyshomeostasis Disrupts Neuronal and Synaptic Function in Alzheimer's Disease.

6. Restoration of Sarcoplasmic Reticulum Ca²⁺ ATPase (SERCA) Activity Prevents Age-Related Muscle Atrophy and Weakness in Mice.

Review 10. Ca²⁺ Dyshomeostasis Disrupts Neuronal and Synaptic Function in Alzheimer's Disease.