Wheat germ agglutinin-conjugated liposomes incorporated with cardiolipin to improve neuronal survival in Alzheimer’s disease treatment

Abstract

Curcumin (CRM) and nerve growth factor (NGF) were entrapped in liposomes (LIP) with surface wheat germ agglutinin (WGA) to downregulate the phosphorylation of kinases in Alzheimer’s disease (AD) therapy. Cardiolipin (CL)-conjugated LIP carrying CRM (CRM-CL/LIP) and also carrying NGF (NGF-CL/LIP) were used with AD models of SK-N-MC cells and Wistar rats after an insult with β-amyloid peptide (Aβ). We found that CRM-CL/LIP inhibited the expression of phosphorylated p38 (p-p38), phosphorylated c-Jun N-terminal kinase (p-JNK), and p-tau protein at serine 202 and prevented neurodegeneration of SK-N-MC cells. In addition, NGF-CL/LIP could enhance the quantities of p-neurotrophic tyrosine kinase receptor type 1 and p-extracellular signal-regulated kinase 5 for neuronal rescue. Moreover, WGA-grafted CRM-CL/LIP and WGA-grafted NGF-CL/LIP significantly improved the permeation of CRM and NGF across the blood–brain barrier, reduced Aβ plaque deposition and the malondialdehyde level, and increased the percentage of normal neurons and cholinergic activity in the hippocampus of AD rats. Based on the marker expressions and in vivo evidence, current LIP carriers can be promising drug delivery systems to protect nervous tissue against Aβ-induced apoptosis in the brain during the clinical management of AD.

Neuroprotection against apoptosis of SK-N-MC cells using RMP-7- and lactoferrin-grafted liposomes carrying quercetin

“…42 Moreover, tau hyperphosphorylation induced by p-JNK and p-p38 is located at S202 in the early stage. 43 It is well known that Figure 2 Delivery of rMP-7-lf-QU-ls across the BBB (r sa =5%). Notes: (A) Viability of BBB cells (hBMecs and has; C rMP-7 =20 μg/ml; C lf =20 μg/ml; n=3); high viability of hBMecs and has suggested that rMP-7-lf-QU-ls could not obviously imperil the BBB structure.…”

Liposome delivery systems for the treatment of Alzheimer’s disease

“…In this case, both PEGylation and WGA provided an additional novel dual functionalization, with the aim of improving delivery across the BBB. 42 WGA-CRM-CL/LIPs reduced Aβ "plaque" deposition in AD model SK-N-MC cells and increased the percentage of healthy neurons with cholinergic activity in a Wistar rat AD model (established by injection of Aβ into CA1 neurons). Additionally, curcumin mediates downstream inhibition of tau phosphorylation at serine 202, which is a key site for axonogenesis ( Figure 6).…”

“…40 Aβ has been shown to insert preferentially into any anionic phospholipids incorporated into liposomes, which could have a protective effect, by removing toxic Aβ. 41,42 The majority of treatments aimed at AD have used PEGylated 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG 2000 (DSPE) to improve circulation time (see "Stealth liposomes" section), although wheat germ agglutinin, chitosan, silk fibroin, and polyvinyl alcohol have also been used to achieve similar "stealth" properties.…”

“…The multifunctional liposomes produced by Kuo et al aim to improve the overall neuronal survival in AD by inhibiting the phosphorylation of p38 and c-Jun N-terminal kinase (JNK), two key members of the mitogen-activated protein kinase (MAPK) family, in neurons damaged by the accumulation of Aβ ( Figure 6). 42 Study of this kinase cascade is essential for the understanding of AD progression, since MAPKcatalyzed phosphorylation events in the brain have a key role in the downstream activity of cellular components (eg, phosphatases, kinases) that impact on apoptosis and overall neuronal survival. It would also provide valuable insight into possible future therapies.…”

Amphiphilic Nanocarrier Systems for Curcumin Delivery in Neurodegenerative Disorders

“…Liposomes functionalized with TAT-peptide In vitro Permeability across the BBB enhanced [98]. Increased entrapment efficiency of NGF and CU, of NGF release and cell viability, Decreased release of CU, Permeability of NGF and CU across the blood-brain barrier [102].…”