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Clioquinol reduces zinc accumulation in neuritic plaques and inhibits the amyloidogenic pathway in AβPP/PS1 transgenic mouse brain.
J Alzheimers Dis. 2012; 29(3):549-59.JA

Abstract

Metal dyshomeostasis in the brain helps promote amyloid-β (Aβ) deposition in Alzheimer's disease (AD). Therefore, targeting the interactions between metal and Aβ is a potential therapeutic approach for AD. The metal chelator, clioquinol (CQ), is thought to reduce Aβ deposits in the AD transgenic mouse brain, and attenuate the clinical symptoms of AD patients. However, whether oral administration of CQ reduces zinc accumulation in Aβ plaques and inhibits the amyloidogenic pathway have not been properly established in AD transgenic mice. By means of autometallographic analysis, we show for the first time that both the number and size of the zinc-containing plaques were significantly reduced in the brain of amyloid-β protein precursor (AβPP)/presenilin 1 (PS1) double transgenic mice treated with CQ (30 mg/kg/day) orally for 2 months. This was accompanied by a reduction in Aβ burden in the CQ-treated mouse brain. Furthermore, CQ treatment markedly reduced the expression levels of AβPP protein, the β-site of AβPP cleaving enzyme 1 (BACE1), PS1, and the secreted β-secretase-derived fragments of AβPP (sAβPPβ). The present data indicate that CQ is able to reduce zinc accumulation in the neuritic plaques and inhibit amyloidogenic AβPP processing in the AβPP/PS1 mouse brain.

Authors+Show Affiliations

Department of Pathophysiology, China Medical University, Shenyang, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22269164

Citation

Wang, Tao, et al. "Clioquinol Reduces Zinc Accumulation in Neuritic Plaques and Inhibits the Amyloidogenic Pathway in AβPP/PS1 Transgenic Mouse Brain." Journal of Alzheimer's Disease : JAD, vol. 29, no. 3, 2012, pp. 549-59.
Wang T, Wang CY, Shan ZY, et al. Clioquinol reduces zinc accumulation in neuritic plaques and inhibits the amyloidogenic pathway in AβPP/PS1 transgenic mouse brain. J Alzheimers Dis. 2012;29(3):549-59.
Wang, T., Wang, C. Y., Shan, Z. Y., Teng, W. P., & Wang, Z. Y. (2012). Clioquinol reduces zinc accumulation in neuritic plaques and inhibits the amyloidogenic pathway in AβPP/PS1 transgenic mouse brain. Journal of Alzheimer's Disease : JAD, 29(3), 549-59. https://doi.org/10.3233/JAD-2011-111874
Wang T, et al. Clioquinol Reduces Zinc Accumulation in Neuritic Plaques and Inhibits the Amyloidogenic Pathway in AβPP/PS1 Transgenic Mouse Brain. J Alzheimers Dis. 2012;29(3):549-59. PubMed PMID: 22269164.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clioquinol reduces zinc accumulation in neuritic plaques and inhibits the amyloidogenic pathway in AβPP/PS1 transgenic mouse brain. AU - Wang,Tao, AU - Wang,Chun-Yan, AU - Shan,Zhong-Yan, AU - Teng,Wei-Ping, AU - Wang,Zhan-You, PY - 2012/1/25/entrez PY - 2012/1/25/pubmed PY - 2012/8/10/medline SP - 549 EP - 59 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 29 IS - 3 N2 - Metal dyshomeostasis in the brain helps promote amyloid-β (Aβ) deposition in Alzheimer's disease (AD). Therefore, targeting the interactions between metal and Aβ is a potential therapeutic approach for AD. The metal chelator, clioquinol (CQ), is thought to reduce Aβ deposits in the AD transgenic mouse brain, and attenuate the clinical symptoms of AD patients. However, whether oral administration of CQ reduces zinc accumulation in Aβ plaques and inhibits the amyloidogenic pathway have not been properly established in AD transgenic mice. By means of autometallographic analysis, we show for the first time that both the number and size of the zinc-containing plaques were significantly reduced in the brain of amyloid-β protein precursor (AβPP)/presenilin 1 (PS1) double transgenic mice treated with CQ (30 mg/kg/day) orally for 2 months. This was accompanied by a reduction in Aβ burden in the CQ-treated mouse brain. Furthermore, CQ treatment markedly reduced the expression levels of AβPP protein, the β-site of AβPP cleaving enzyme 1 (BACE1), PS1, and the secreted β-secretase-derived fragments of AβPP (sAβPPβ). The present data indicate that CQ is able to reduce zinc accumulation in the neuritic plaques and inhibit amyloidogenic AβPP processing in the AβPP/PS1 mouse brain. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/22269164/Clioquinol_reduces_zinc_accumulation_in_neuritic_plaques_and_inhibits_the_amyloidogenic_pathway_in_A������PP/PS1_transgenic_mouse_brain_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-2011-111874 DB - PRIME DP - Unbound Medicine ER -