Fatty acids increase presenilin-1 levels and γ-secretase activity in PSwt-1 cells

Liu, Yanzhu; Yang, Lin; Conde-Knape, Karin; Beher, Dirk; Shearman, Mark S.; Shachter, Neil S.

doi:10.1194/jlr.m400317-jlr200

Cited by 36 publications

(26 citation statements)

References 59 publications

(57 reference statements)

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“…In general, the remaining inhibitory molecules have structural similarity with fatty acids and small phospholipids, which have been shown to modulate aggregation of A␤. Indeed, several published epidemiological studies suggest that high levels of docosahexanoic acid are associated with positive effects in Alzheimer disease sufferers (39,40). Furthermore, -3 unsaturated fatty acids have a neuroprotective effect, and it has been suggested that a diet rich in these forms of fatty acids may aid in the prevention of Alzheimer disease (41).…”

Section: Tablementioning

confidence: 99%

Small Amphipathic Molecules Modulate Secondary Structure and Amyloid Fibril-forming Kinetics of Alzheimer Disease Peptide Aβ1–42

Ryan

Friedhuber

Lind

et al. 2012

Journal of Biological Chemistry

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Background: A␤ aggregation may be modulated by small lipid-like molecules. Results: Activators induced ␤-structure and rapid aggregation, whereas inhibitors induced ␣-helical structure and small A␤ oligomers. Conclusion: Small lipid-like molecules modulate A␤ secondary structure and self-association at stoichiometric levels. Significance: Understanding the role of small molecules and lipids in Alzheimer disease is crucial for the development of effective therapeutic targets.

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Section: Tablementioning

confidence: 99%

Small Amphipathic Molecules Modulate Secondary Structure and Amyloid Fibril-forming Kinetics of Alzheimer Disease Peptide Aβ1–42

Ryan

Friedhuber

Lind

et al. 2012

Journal of Biological Chemistry

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“…In another study, elevated blood triacylglycerol levels preceded amyloid deposition in mouse brain [133]. It has been shown that fatty acids can cause generation of presenilin-1, an important determinate of γ -secretase activity necessary for generation of Aβ in neuroblastoma cells [134]. Furthermore, palmitic and stearic fatty acids [SFAs (saturated fatty acids)] induce AD-like hyperphosphorylation of Tau in primary rat cortical neurons [135].…”

Section: Triacylglycerols Fatty Acids and The Initiation And Progresmentioning

confidence: 99%

The vascular contribution to Alzheimer's disease

2010

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AD (Alzheimer’s disease) is a progressive neurodegenerative disease of unknown origin. Despite questions as to the underlying cause(s) of this disease, shared risk factors for both AD and atherosclerotic cardiovascular disease indicate that vascular mechanisms may critically contribute to the development and progression of both AD and atherosclerosis. An increased risk of developing AD is linked to the presence of the apoE4 (apolipoprotein E4) allele, which is also strongly associated with increased risk of developing atherosclerotic cardiovascular disease. Recent studies also indicate that cardiovascular risk factors, including elevated blood cholesterol and triacylglycerol (triglyceride), increase the likelihood of AD and vascular dementia. Lipids and lipoproteins in the circulation interact intimately with the cerebrovasculature, and may have important effects on its constituent brain microvascular endothelial cells and the adjoining astrocytes, which are components of the neurovascular unit. The present review will examine the potential mechanisms for understanding the contributions of vascular factors, including lipids, lipoproteins and cerebrovascular Aβ (amyloid β), to AD, and suggest therapeutic strategies for the attenuation of this devastating disease process. Specifically, we will focus on the actions of apoE, TGRLs (triacylglycerol-rich lipoproteins) and TGRL lipolysis products on injury of the neurovascular unit and increases in blood–brain barrier permeability.

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“…At the same time, the study of the effects of fatty acids on cell membrane fluidity and sA β PP α secretion in relation to degrees of unsaturation has suggested that not all unsaturated fatty acids, but only those with 4 or more double bonds, such as arachidonic acid (20 : 4), eicosapentaenoic acid (20 : 5), and DHA (22 : 6), increased membrane fluidity and led to an increase in sA β PP α secretion, while oleic acid (18 : 1), linoleic acid (18 : 2), and α -linolenic acid (18 : 3) did not [113]. Moreover, the results of another experiment have indicated that treatment of PSwt-1 cells with oleic acid and linoleic acid increased γ -secretase activity and A β production [123]. …”

Section: Role Of Physical Membrane Properties In Aβpp Processingmentioning

confidence: 99%

Impacts of Membrane Biophysics in Alzheimer′s Disease: From Amyloid Precursor Protein Processing to Aβ Peptide‐Induced Membrane Changes

Askarova

Yang

Lee

2011

International Journal of Alzheimer's Disease

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An increasing amount of evidence supports the notion that cytotoxic effects of amyloid-β peptide (Aβ), the main constituent of senile plaques in Alzheimer's disease (AD), are strongly associated with its ability to interact with membranes of neurons and other cerebral cells. Aβ is derived from amyloidogenic cleavage of amyloid precursor protein (AβPP) by β- and γ-secretase. In the nonamyloidogenic pathway, AβPP is cleaved by α-secretases. These two pathways compete with each other, and enhancing the non-amyloidogenic pathway has been suggested as a potential pharmacological approach for the treatment of AD. Since AβPP, α-, β-, and γ-secretases are membrane-associated proteins, AβPP processing and Aβ production can be affected by the membrane composition and properties. There is evidence that membrane composition and properties, in turn, play a critical role in Aβ cytotoxicity associated with its conformational changes and aggregation into oligomers and fibrils. Understanding the mechanisms leading to changes in a membrane's biophysical properties and how they affect AβPP processing and Aβ toxicity should prove to provide new therapeutic strategies for prevention and treatment of AD.

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Fatty acids increase presenilin-1 levels and γ-secretase activity in PSwt-1 cells

Cited by 36 publications

References 59 publications

Small Amphipathic Molecules Modulate Secondary Structure and Amyloid Fibril-forming Kinetics of Alzheimer Disease Peptide Aβ1–42

Small Amphipathic Molecules Modulate Secondary Structure and Amyloid Fibril-forming Kinetics of Alzheimer Disease Peptide Aβ1–42

The vascular contribution to Alzheimer's disease

Impacts of Membrane Biophysics in Alzheimer′s Disease: From Amyloid Precursor Protein Processing to Aβ Peptide‐Induced Membrane Changes

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