Ion channel formation by Alzheimer's disease amyloid β-peptide (Aβ40) in unilamellar liposomes is determined by anionic phospholipids

Alarcón, Juan Marcos; Brito, Julio A.; Hermosilla, Tamara; Atwater, I; Mears, David; Rojas, Eduardo

doi:10.1016/j.peptides.2005.07.004

Cited by 64 publications

(53 citation statements)

References 59 publications

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“…Consequently, the early increase in synaptic transmitter release by A␤ was associated with the rise in intracellular calcium, in agreement with previous studies on liposomes and clonal cell lines (21,22). This increase might depend on voltage-gated calcium channels (40), AMPA receptors (38), NMDA receptors (8), or formation of calcium-permeable membrane pores (21,22,32,41). Our data showed that antagonists for calcium channels, NMDA and AMPA receptors were unable to block the A␤-induced increase in intracellular calcium, although it was blocked by Na7, a small peptide reported to block calcium influx, through the amyloid pore (34,42).…”

Section: Effects Of Low A␤ Concentrations On Synaptic Transmission-supporting

confidence: 92%

Section: Effects Of Low A␤ Concentrations On Synaptic Transmission-supporting

confidence: 90%

“…Acute A␤ Increased Intracellular Calcium, Vesicle Release, and Synaptic Transmission-A␤ was shown to increase intracellular calcium in non-neuronal cells (21,22). In agreement, short (60-s) applications of A␤ (500 nM-5 M) with a puffer pipette induced a rapid and reversible increase in intracellular calcium in hippocampal neurons (Fig.…”

Section: Early Effects Of A␤ On Presynaptic Proteins-confocalsupporting

confidence: 73%

“…The ultrastructural forms (oligomers and short fibrils) that appeared after 120 -150 min of agitation, corresponding to the neuroactive A␤ forms, were structurally (Fig. 1Db) and functionally similar to a heterogeneous array of forms defined as oligomers, protofibrils, and A␤-derived diffusible ligands, known to enhance neuronal spiking and intracellular calcium (14,20,21). These features were not observed in either nonaggregated peptide (monomers) (Fig.…”

Section: Effects Of Chronic A␤ On Synaptic Transmission In Hippocam-mentioning

confidence: 91%

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β-Amyloid Causes Depletion of Synaptic Vesicles Leading to Neurotransmission Failure

Parodí

Sepúlveda

Roa

et al. 2010

Journal of Biological Chemistry

164

120

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Alzheimer disease is a progressive neurodegenerative brain disorder that leads to major debilitating cognitive deficits. It is believed that the alterations capable of causing brain circuitry dysfunctions have a slow onset and that the full blown disease may take several years to develop. Therefore, it is important to understand the early, asymptomatic, and possible reversible states of the disease with the aim of proposing preventive and disease-modifying therapeutic strategies. It is largely unknown how amyloid ␤-peptide (A␤), a principal agent in Alzheimer disease, affects synapses in brain neurons. In this study, we found that similar to other pore-forming neurotoxins, A␤ induced a rapid increase in intracellular calcium and miniature currents, indicating an enhancement in vesicular transmitter release. Significantly, blockade of these effects by low extracellular calcium and a peptide known to act as an inhibitor of the A␤-induced pore prevented the delayed failure, indicating that A␤ blocks neurotransmission by causing vesicular depletion. This new mechanism for A␤ synaptic toxicity should provide an alternative pathway to search for small molecules that can antagonize these effects of A␤.

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Section: Effects Of Low A␤ Concentrations On Synaptic Transmission-supporting

confidence: 92%

Section: Effects Of Low A␤ Concentrations On Synaptic Transmission-supporting

confidence: 90%

Section: Early Effects Of A␤ On Presynaptic Proteins-confocalsupporting

confidence: 73%

Section: Effects Of Chronic A␤ On Synaptic Transmission In Hippocam-mentioning

confidence: 91%

See 2 more Smart Citations

β-Amyloid Causes Depletion of Synaptic Vesicles Leading to Neurotransmission Failure

Parodí

Sepúlveda

Roa

et al. 2010

Journal of Biological Chemistry

164

120

View full text Add to dashboard Cite

show abstract

“…Aβ peptide needs anionic phospholipids for binding and insertion into membranes [96][97][98][99][100][101]. Monomeric form does not interact with membranes.…”

Section: Oligomeric State Related Membrane Interactionsmentioning

confidence: 99%

Structure and Function of Stefin B Oligomers – Important Role in Amyloidogenesis

Taler‐Verčič¹,

Polajnar²,

Žerovnik³

2014

Oligomerization of Chemical and Biological Compounds

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Nanomaterials that Aid in the Diagnosis and Treatment of Alzheimer's Disease, Resolving Blood–Brain Barrier Crossing Ability

Song,

Li,

et al. 2024

Advanced Science

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As a form of dementia, Alzheimer's disease (AD) suffers from no efficacious cure, yet AD treatment is still imperative, as it ameliorates the symptoms or prevents it from deteriorating or maintains the current status to the longest extent. The human brain is the most sensitive and complex organ in the body, which is protected by the blood–brain barrier (BBB). This yet induces the difficulty in curing AD as the drugs or nanomaterials that are much inhibited from reaching the lesion site. Thus, BBB crossing capability of drug delivery system remains a significant challenge in the development of neurological therapeutics. Fortunately, nano‐enabled delivery systems possess promising potential to achieve multifunctional diagnostics/therapeutics against various targets of AD owing to their intriguing advantages of nanocarriers, including easy multifunctionalization on surfaces, high surface‐to‐volume ratio with large payloads, and potential ability to cross the BBB, making them capable of conquering the limitations of conventional drug candidates. This review, which focuses on the BBB crossing ability of the multifunctional nanomaterials in AD diagnosis and treatment, will provide an insightful vision that is conducive to the development of AD‐related nanomaterials.

show abstract

Ion channel formation by Alzheimer's disease amyloid β-peptide (Aβ40) in unilamellar liposomes is determined by anionic phospholipids

Cited by 64 publications

References 59 publications

β-Amyloid Causes Depletion of Synaptic Vesicles Leading to Neurotransmission Failure

β-Amyloid Causes Depletion of Synaptic Vesicles Leading to Neurotransmission Failure

Structure and Function of Stefin B Oligomers – Important Role in Amyloidogenesis

Nanomaterials that Aid in the Diagnosis and Treatment of Alzheimer's Disease, Resolving Blood–Brain Barrier Crossing Ability

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