Anapsos: New Therapeutic Strategies for Neurodegeneration and Brain Aging with Neuroimmunotrophic Factors

Alvarez, X.A.; Zas, R.; Lagares, R.; Fernández‐Novoa, L.; Franco-Maside, A.; Miguel-Hidalgo, José Javier; Cacabelos, Ramón; Díaz, Joaquín; Sempere, J.

doi:10.1007/978-1-4612-4116-4_55

Cited by 4 publications

(9 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the nonamyloidgenic pathway, N-terminal truncated Aβ 11/17-40/42 (known as p3) and Aβ 9-42 (known as N9) are produced by β′/γ-secretases and α/γ-secretases, respectively. A number of in vitro and in vivo studies have shown that introduction of the full-length Aβ, p3, or N9 peptides to cultured cells and living tissues can induce the damage of their functions and viability 11, 12 . Moreover, other Aβ fragments such as Aβ 25-35 , Aβ 1-28 , and Aβ 29-40 have also been found to have similar amyloidgenic properties to full-length Aβ by forming morphologically similar amyloid fibrils, inducing neurodegeneration and cellular apoptosis, and impairing learning and memory functions 13, 14 .…”

Section: Introductionmentioning

confidence: 99%

Molecular interactions of Alzheimer amyloid-β oligomers with neutral and negatively charged lipid bilayers

Wang

Pan

et al. 2013

Phys. Chem. Chem. Phys.

View full text Add to dashboard Cite

Interaction of p3 (Aβ17-42) peptides with cell membrane is crucial for the understanding of amyloid toxicity associated with Alzheimer’s disease (AD). Such p3-membrane interactions are considered to induce the disruption of membrane permeability and integrity, but the exact mechanisms of how p3 aggregates, particularly small p3 oligomers, induce receptor-independent membrane disruption are not yet completely understood. Here, we investigate the adsorption, orientation, and surface interaction of the p3 pentamer with lipid bilayers composed of both pure zwitterionic POPC (palmitoyl-oleyl-phosphatidylcholine) and mixed anionic POPC/POPG (palmitoyl-oleyl-phosphatidylglycerol) (3:1) lipids using explicit-solvent molecular dynamics (MD) simulations. MD simulation results show that the p3 pentamer has much stronger interactions with mixed POPC/POPG lipids than pure POPC lipids, consistent with experimental observation that Aβ adsorption and fibrililation are enhanced on anionic lipid bilayers. Although electrostatic interactions are main attractive forces to drive the p3 to adsorb on the bilayer surface, the adsorption of the p3 pentamer on the lipid bilayer with a preferential C-terminal β-strands facing toward the bilayer surface is a net outcome of different competitions between p3 peptides-lipid bilayer and ions-p3-bilayer interactions. More importantly, Ca2+ ions are found to form ionic bridges to associate negatively charged residues of p3 with anionic headgroups of the lipid bilayer, resulting in Aβ–Ca2+–PO4− complexes. Intensive Ca2+ bound to lipid bilayer and Ca2+ ionic bridges may lead to the alternation of Ca2+ hemostasis responsible for neuronal dysfunction and death. This work provides insights into the mutual structure, dynamics, and interactions of both Aβ peptides and lipid bilayer at the atomic level, which expand our understanding of the complex behavior of amyloid-induced membrane disruption.

show abstract

Section: Introductionmentioning

confidence: 99%

Molecular interactions of Alzheimer amyloid-β oligomers with neutral and negatively charged lipid bilayers

Wang

Pan

et al. 2013

Phys. Chem. Chem. Phys.

View full text Add to dashboard Cite

show abstract

“…10). The daily administration of anapsos improved PAL in a manner similar to that of animals with nbM lesions (4,8,10). Taking into account that transplants of peripheral cholinergic neurons or fetal cholinergic-rich brain tissue and the administration of physostigmine antagonize cog- nitive impairments in rats with nbM lesions (lo), it is possible that anapsos-induced learning improvement is mediated by restoration of the brain cholinergic activity in these animals.…”

Section: Nbm-lesioned Animalsmentioning

confidence: 88%

“…Recently, it has also been reported that p-AP injections produce hippocampal neurodegeneration and neurotoxicity of cholinergic and noradrenergic fibers in the vicinity of the lesion (8,39,48,56).…”

Section: Rats With P-ap Implants Into the Hippocampusmentioning

confidence: 98%

“…Eleven-month-old Swiss-Webster mice (N = 6 mice/group) received anapsos 0, 25, or 100 mg/kg/d subcutaneously (s.c.) for 11 months. Brain IL-1 p and histamine concentrations were measured in the surviving mice (8). In this study, the chronic administration of anapsos induced a dose-dependent increase in cortical IL-lp with no change in hypothalamic or hippocampal levels of the cytokine (Fig.…”

Section: Effects In Old Micementioning

confidence: 99%

“…Neuroimmunotrophic effects of anapsos have also been demonstrated in old mice treated chronically with the extract (8). Eleven-month-old Swiss-Webster mice (N = 6 mice/group) received anapsos 0, 25, or 100 mg/kg/d subcutaneously (s.c.) for 11 months.…”

Section: Effects In Old Micementioning

confidence: 99%

See 2 more Smart Citations

Anapsos: Neuroimmunotrophic Treatment in Alzheimer Disease and Neurodegenerative Disorders

et al. 1997

Self Cite

View full text Add to dashboard Cite

Anapsos Improves Learning and Memory in Rats with βA(1–28) Deposits Into the Hippocampus

Álvarez

Miguel-Hidalgo

Fernández‐Novoa

et al. 1998

Advances in Behavioral Biology

View full text Add to dashboard Cite

Anapsos: New Therapeutic Strategies for Neurodegeneration and Brain Aging with Neuroimmunotrophic Factors

Cited by 4 publications

References 5 publications

Molecular interactions of Alzheimer amyloid-β oligomers with neutral and negatively charged lipid bilayers

Molecular interactions of Alzheimer amyloid-β oligomers with neutral and negatively charged lipid bilayers

Anapsos: Neuroimmunotrophic Treatment in Alzheimer Disease and Neurodegenerative Disorders

Anapsos Improves Learning and Memory in Rats with βA(1–28) Deposits Into the Hippocampus

Contact Info

Product

Resources

About