Transducible P11-CNTF rescues the learning and memory impairments induced by amyloid-beta peptide in mice

Qu, Heng Yan; Zhang, Ting; Li, Xu Ling; Zhou, Jian; Zhao, Bao Quan; Li, Qian; Sun, Mingjun

doi:10.1016/j.ejphar.2008.06.109

Cited by 19 publications

(13 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ECE expression and activity correlates well with A β deposition and the onset of AD [16,65–68], and data from cultured cells and animal model indicated that A β is a physiologically relevant substrate of ECE [16]. Animals lacking ECE-2 are deficient in learning and memory [69].…”

Section: Discussionmentioning

confidence: 99%

Effects of 4-Hydroxy-Nonenal and Amyloid-β on Expression and Activity of Endothelin Converting Enzyme and Insulin Degrading Enzyme in SH-SY5Y Cells

Wang

Malter

et al. 2009

JAD

View full text Add to dashboard Cite

The cerebral accumulation of amyloid-β (Aβ) is a consistent feature of and likely contributor to the development of Alzheimer's disease (AD). In addition to dysregulated production, increasing experimental evidence suggests reduced catabolism plays an important role in Aβ accumulation. Although endothelin converting enzyme (ECE) and insulin degrading enzyme (IDE) degrade and thus contribute to regulating the steady-state levels of Aβ, how these enzymes are regulated remain poorly understood. In this study, we investigated the effects of 4-hydroxy-nonenal (HNE) and Aβ on the expression and activity of ECE-1 and IDE in human neuroblastoma SH-SY5Y cells. Treatment with HNE or Aβ upregulated ECE-1 mRNA and protein, while IDE was unchanged. Although both ECE-1 and IDE were oxidized within 24 h of HNE or Aβ treatment, ECE-1 catalytic activity was elevated while IDE specific activity was unchanged. The results demonstrated for the first time that both ECE-1 and IDE are substrates of HNE modification induced by Aβ. In addition, the results suggest complex mechanisms underlying the regulation of their enzymatic activity.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of 4-Hydroxy-Nonenal and Amyloid-β on Expression and Activity of Endothelin Converting Enzyme and Insulin Degrading Enzyme in SH-SY5Y Cells

Wang

Malter

et al. 2009

JAD

View full text Add to dashboard Cite

show abstract

“…For clinical use, NTF administration must be delivered centrally in appropriate quantities to effectively stimulate neurons over a prolonged time period and to avoid intolerable side effects (Nagahara et al, 2009). A recent study showed that a transducible form of CNTF rescued mice from infused fibrillar A␤ (Qu et al, 2008). However, the doses of CNTF were high (i.e., 100 g ⅐ kg Ϫ1 ⅐ d Ϫ1 ), and only short-term treatment effects were investigated.…”

Section: Discussionmentioning

confidence: 99%

Ciliary Neurotrophic Factor Cell-Based Delivery Prevents Synaptic Impairment and Improves Memory in Mouse Models of Alzheimer's Disease

Garcia¹,

Youssef²,

Utvik³

et al. 2010

J. Neurosci.

116

View full text Add to dashboard Cite

The development of novel therapeutic strategies for Alzheimer's disease (AD) represents one of the biggest unmet medical needs today. Application of neurotrophic factors able to modulate neuronal survival and synaptic connectivity is a promising therapeutic approach for AD. We aimed to determine whether the loco-regional delivery of ciliary neurotrophic factor (CNTF) could prevent amyloid-␤ (A␤) oligomer-induced synaptic damages and associated cognitive impairments that typify AD. To ensure long-term administration of CNTF in the brain, we used recombinant cells secreting CNTF encapsulated in alginate polymers. The implantation of these bioreactors in the brain of A␤ oligomer-infused mice led to a continuous secretion of recombinant CNTF and was associated with the robust improvement of cognitive performances. Most importantly, CNTF led to full recovery of cognitive functions associated with the stabilization of synaptic protein levels in the Tg2576 AD mouse model. In vitro as well as in vivo, CNTF activated a Janus kinase/signal transducer and activator of transcription-mediated survival pathway that prevented synaptic and neuronal degeneration. These preclinical studies suggest that CNTF and/or CNTF receptor-associated pathways may have AD-modifying activity through protection against progressive A␤-related memory deficits. Our data also encourage additional exploration of ex vivo gene transfer for the prevention and/or treatment of AD.

show abstract

“…Lower than normal BDNF levels have been linked to neuronal loss in epilepsy (Azoulay, Urshansky, & Karni, 2008), and declines in BDNF, BDNF mRNA and/or proBDNF play a role in the pathologic changes in both aging and Alzheimer's diseased brains (Tapia-Arancibia et al, 2008). CNTF treatment of mouse models of both Alzheimer's and Huntington's disease results in rescue of learning and memory impairments (Emerich et al, 1997; Qu et al, 2008). After traumatic brain injury, treatment of the hippocampus with NT-4 reduces neuronal loss in pyramidal cells (Royo et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Intranasal delivery of neurotrophic factors BDNF, CNTF, EPO, and NT-4 to the CNS

Alcala-Barraza

Lee

Hanson

et al. 2009

Journal of Drug Targeting

148

View full text Add to dashboard Cite

Injury to the central nervous system (CNS) generally results in significant neuronal death and functional loss. In vitro experiments have demonstrated that neurotrophic factors such as brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and neurotrophin-4/5 (NT-4/5) can promote neuronal survival. However, delivery to the injured CNS is difficult as these large protein molecules do not efficiently cross the blood–brain barrier. Intranasal delivery of 70 μg [125I]-radiolabeled BDNF, CNTF, NT-4, or erythropoietin (EPO) resulted in 0.1–1.0 nM neurotrophin concentrations within 25 min in brain parenchyma. In addition, not only did these neurotrophic factors reach the CNS, they were present in sufficient concentrations to activate the prosurvival PI3Kinase/Akt pathway, even where lower levels of neurotrophic factors were measured. Currently traumatic, ischemic and compressive injuries to the CNS have no effective treatment. There is potential clinical relevancy of this method for rescuing injured CNS tissues in order to maintain CNS function in affected patients. The intranasal delivery method has great clinical potential due to (1) simplicity of administration, (2) noninvasive drug administration, (3) relatively rapid CNS delivery, (4) ability to repeat dosing easily, (5) no requirement for drug modification, and (6) minimal systemic exposure.

show abstract

Transducible P11-CNTF rescues the learning and memory impairments induced by amyloid-beta peptide in mice

Cited by 19 publications

References 53 publications

Effects of 4-Hydroxy-Nonenal and Amyloid-β on Expression and Activity of Endothelin Converting Enzyme and Insulin Degrading Enzyme in SH-SY5Y Cells

Effects of 4-Hydroxy-Nonenal and Amyloid-β on Expression and Activity of Endothelin Converting Enzyme and Insulin Degrading Enzyme in SH-SY5Y Cells

Ciliary Neurotrophic Factor Cell-Based Delivery Prevents Synaptic Impairment and Improves Memory in Mouse Models of Alzheimer's Disease

Intranasal delivery of neurotrophic factors BDNF, CNTF, EPO, and NT-4 to the CNS

Contact Info

Product

Resources

About