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Clioquinol decreases amyloid-beta burden and reduces working memory impairment in a transgenic mouse model of Alzheimer's disease.
J Alzheimers Dis 2009; 17(2):423-40JA

Abstract

Clioquinol (CQ) is a "metal protein attenuating compound" that crosses the blood-brain barrier and binds, with high affinity, copper(II) and zinc(II), two metal ions critically involved in amyloid-beta aggregation and toxicity. CQ was recently proposed for the treatment of Alzheimer's disease, but controversial data have been reported so far concerning its real therapeutic advantages. We describe here results of chronic CQ treatment in the TgCRND8 mouse model of Alzheimer's disease. Remarkably, based on classical behavioral tests, CQ treatment was found to reverse, to a large extent, the working memory impairments that are characteristic of this mouse model. Pairwise, a significant reduction of amyloid-beta plaque burden, both in the cortex and in the hippocampus, was detected as well as an attenuation of astrogliosis. MALDI Mass Spectrometry Imaging technique revealed a specific localization of CQ in the above mentioned brain areas. Modest but significant effects on the absolute and relative brain concentrations of the three most important biometals (i.e., copper, zinc, and iron) were highlighted following CQ treatment. The pharmacological and mechanistic implications of the above findings are thoroughly discussed.

Authors+Show Affiliations

Department of Pharmacology, University of Florence, Florence, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

19363260

Citation

Grossi, Cristina, et al. "Clioquinol Decreases Amyloid-beta Burden and Reduces Working Memory Impairment in a Transgenic Mouse Model of Alzheimer's Disease." Journal of Alzheimer's Disease : JAD, vol. 17, no. 2, 2009, pp. 423-40.
Grossi C, Francese S, Casini A, et al. Clioquinol decreases amyloid-beta burden and reduces working memory impairment in a transgenic mouse model of Alzheimer's disease. J Alzheimers Dis. 2009;17(2):423-40.
Grossi, C., Francese, S., Casini, A., Rosi, M. C., Luccarini, I., Fiorentini, A., ... Casamenti, F. (2009). Clioquinol decreases amyloid-beta burden and reduces working memory impairment in a transgenic mouse model of Alzheimer's disease. Journal of Alzheimer's Disease : JAD, 17(2), pp. 423-40. doi:10.3233/JAD-2009-1063.
Grossi C, et al. Clioquinol Decreases Amyloid-beta Burden and Reduces Working Memory Impairment in a Transgenic Mouse Model of Alzheimer's Disease. J Alzheimers Dis. 2009;17(2):423-40. PubMed PMID: 19363260.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clioquinol decreases amyloid-beta burden and reduces working memory impairment in a transgenic mouse model of Alzheimer's disease. AU - Grossi,Cristina, AU - Francese,Simona, AU - Casini,Angela, AU - Rosi,Maria Cristina, AU - Luccarini,Ilaria, AU - Fiorentini,Anna, AU - Gabbiani,Chiara, AU - Messori,Luigi, AU - Moneti,Gloriano, AU - Casamenti,Fiorella, PY - 2009/4/14/entrez PY - 2009/4/14/pubmed PY - 2009/12/17/medline SP - 423 EP - 40 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 17 IS - 2 N2 - Clioquinol (CQ) is a "metal protein attenuating compound" that crosses the blood-brain barrier and binds, with high affinity, copper(II) and zinc(II), two metal ions critically involved in amyloid-beta aggregation and toxicity. CQ was recently proposed for the treatment of Alzheimer's disease, but controversial data have been reported so far concerning its real therapeutic advantages. We describe here results of chronic CQ treatment in the TgCRND8 mouse model of Alzheimer's disease. Remarkably, based on classical behavioral tests, CQ treatment was found to reverse, to a large extent, the working memory impairments that are characteristic of this mouse model. Pairwise, a significant reduction of amyloid-beta plaque burden, both in the cortex and in the hippocampus, was detected as well as an attenuation of astrogliosis. MALDI Mass Spectrometry Imaging technique revealed a specific localization of CQ in the above mentioned brain areas. Modest but significant effects on the absolute and relative brain concentrations of the three most important biometals (i.e., copper, zinc, and iron) were highlighted following CQ treatment. The pharmacological and mechanistic implications of the above findings are thoroughly discussed. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/19363260/Clioquinol_decreases_amyloid_beta_burden_and_reduces_working_memory_impairment_in_a_transgenic_mouse_model_of_Alzheimer's_disease_ L2 - https://content.iospress.com/openurl?genre=article&issn=1387-2877&volume=17&issue=2&spage=423 DB - PRIME DP - Unbound Medicine ER -