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Indirubin-3'-monoxime rescues spatial memory deficits and attenuates beta-amyloid-associated neuropathology in a mouse model of Alzheimer's disease.
Neurobiol Dis 2010; 39(2):156-68ND

Abstract

Indirubin and its derivatives have been shown to possess potent inhibitory effects on cyclin-dependent protein kinase 5 and glycogen synthase kinase 3beta, two protein kinases involved in abnormal hyperphosphorylation of tau and amyloid precursor protein processing/beta-amyloid (Abeta) production. Here, we showed that systemic treatment of APP and presenilin 1 (PS1) transgenic mice, a robust Alzheimer's disease (AD) mouse model, with indirubin-3'-monoxime (IMX; 20mg/kg; 3 times weekly), for as little as 2months, significantly attenuated spatial memory deficits. This was accompanied by a marked decrease in several AD-like phenotypes, including Abeta deposition, tau hyperphosphorylation, accumulation of activated microglia and astrocytes around Abeta plaques, and loss of synaptophysin immunoreactivity. These findings suggest that IMX is a potential therapeutic agent to combat AD.

Authors+Show Affiliations

Department of Veterans Affairs Medical Center, Richmond, VA 23249, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20381617

Citation

Ding, Yun, et al. "Indirubin-3'-monoxime Rescues Spatial Memory Deficits and Attenuates Beta-amyloid-associated Neuropathology in a Mouse Model of Alzheimer's Disease." Neurobiology of Disease, vol. 39, no. 2, 2010, pp. 156-68.
Ding Y, Qiao A, Fan GH. Indirubin-3'-monoxime rescues spatial memory deficits and attenuates beta-amyloid-associated neuropathology in a mouse model of Alzheimer's disease. Neurobiol Dis. 2010;39(2):156-68.
Ding, Y., Qiao, A., & Fan, G. H. (2010). Indirubin-3'-monoxime rescues spatial memory deficits and attenuates beta-amyloid-associated neuropathology in a mouse model of Alzheimer's disease. Neurobiology of Disease, 39(2), pp. 156-68. doi:10.1016/j.nbd.2010.03.022.
Ding Y, Qiao A, Fan GH. Indirubin-3'-monoxime Rescues Spatial Memory Deficits and Attenuates Beta-amyloid-associated Neuropathology in a Mouse Model of Alzheimer's Disease. Neurobiol Dis. 2010;39(2):156-68. PubMed PMID: 20381617.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Indirubin-3'-monoxime rescues spatial memory deficits and attenuates beta-amyloid-associated neuropathology in a mouse model of Alzheimer's disease. AU - Ding,Yun, AU - Qiao,Aimin, AU - Fan,Guo-Huang, Y1 - 2010/04/08/ PY - 2009/10/18/received PY - 2010/03/26/revised PY - 2010/03/29/accepted PY - 2010/4/13/entrez PY - 2010/4/13/pubmed PY - 2010/9/11/medline SP - 156 EP - 68 JF - Neurobiology of disease JO - Neurobiol. Dis. VL - 39 IS - 2 N2 - Indirubin and its derivatives have been shown to possess potent inhibitory effects on cyclin-dependent protein kinase 5 and glycogen synthase kinase 3beta, two protein kinases involved in abnormal hyperphosphorylation of tau and amyloid precursor protein processing/beta-amyloid (Abeta) production. Here, we showed that systemic treatment of APP and presenilin 1 (PS1) transgenic mice, a robust Alzheimer's disease (AD) mouse model, with indirubin-3'-monoxime (IMX; 20mg/kg; 3 times weekly), for as little as 2months, significantly attenuated spatial memory deficits. This was accompanied by a marked decrease in several AD-like phenotypes, including Abeta deposition, tau hyperphosphorylation, accumulation of activated microglia and astrocytes around Abeta plaques, and loss of synaptophysin immunoreactivity. These findings suggest that IMX is a potential therapeutic agent to combat AD. SN - 1095-953X UR - https://www.unboundmedicine.com/medline/citation/20381617/Indirubin_3'_monoxime_rescues_spatial_memory_deficits_and_attenuates_beta_amyloid_associated_neuropathology_in_a_mouse_model_of_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-9961(10)00094-X DB - PRIME DP - Unbound Medicine ER -