Cognitive recovery and restoration of cell proliferation in the dentate gyrus in the 5XFAD transgenic mice model of Alzheimer’s disease following 2-hydroxy-DHA treatment

Fiol-deRoque, María A.; Gutiérrez-Lanza, Raquel; Terés, Silvia; Torres, M.; Barceló, P; Rial, Rubén V.; Verkhratsky, Alexei; Escribá, Pablo V.; Busquets, Xavier; Rodrı́guez, José J.

doi:10.1007/s10522-013-9461-4

Cited by 48 publications

(46 citation statements)

References 67 publications

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“…Upon normalization of the membrane lipid composition by HDHA treatment, the membrane structure recovers the presence of liquid-disordered prone membrane structures [158] (Figure 4). These lipid changes are paralleled with a reduction in Aβ accumulation and tau hyperphosphorylation, and recovery of cognitive scores in a transgenic mouse model of AD (5xFAD mice) [159,160] (see Figure 4).…”

Section: Therapeutic Approaches Based On Pufasmentioning

confidence: 90%

“…HDHA also enhances the survival of neuron-like cells exposed to different insults, such as oligomeric Aβ and NMDA-mediated neurotoxicity (in vitro), and it promotes hippocampal neuronal cell proliferation in 5XFAD mice in vivo [159,160], suggesting that HDHA induced neuroregeneration both in vivo and in vitro, which in part may explain its efficacy against neurodegeneration and memory loss. As part of its mechanism of action, HDHA dampens the binding affinity of oligomeric and fibrillar Aβ to lipid-raft membrane domains.…”

Section: Therapeutic Approaches Based On Pufasmentioning

confidence: 99%

“…Together, this evidence supports a neuroprotective role of HDHA that may be associated with the improved cognitive capabilities observed in AD mice. Adapted from [159,160].…”

Section: Therapeutic Approaches Based On Pufasmentioning

confidence: 99%

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Brain Lipids in the Pathophysiology and Treatment of Alzheimer’s Disease

Torres¹,

Busquets²,

Escribá³

2016

Update on Dementia

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Alzheimer's disease (AD) is a neurodegenerative disorder that causes severe and progressive cognitive impairment. The discovery of specific mutations related to AD supported the amyloid cascade hypothesis, which postulates that the accumulation of the amyloid-β (Aβ) peptide triggers neuronal death and dementia. However, most drugs that aim to prevent Aβ accumulation or tau phosphorylation have consistently failed in clinical trials. This would suggest that the amyloid pathology lies downstream of (an)other cellular event(s) that is/are responsible for AD pathogenesis. In this context, several lipid alterations have been described in the brain and in peripheral fluids of patients with AD, suggesting the involvement of lipids in the etiology of this condition. Indeed, the central nervous system (CNS) has the highest lipid content in the body, next to adipose tissue, and it is thought that normalization of brain membrane lipid levels would revert AD-related pathogenic events. In this sense, novel hydroxylated derivatives of docosahexaenoic acid (DHA) such as natural resolvins or synthetic hydroxy-DHA (HDHA, DHALifort) can modulate membrane lipid composition and show remarkable beneficial effects on AD hallmarks, such as prevention of amyloid production and tau phosphorylation, and cognitive restoration in animal models. Therefore, normalization of the neuronal lipid environment by hydroxyl-DHA and/or other lipids may constitute a promising therapy for AD treatment, memory loss and, possibly, other types of dementia.

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Section: Therapeutic Approaches Based On Pufasmentioning

confidence: 90%

Section: Therapeutic Approaches Based On Pufasmentioning

confidence: 99%

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Brain Lipids in the Pathophysiology and Treatment of Alzheimer’s Disease

Torres¹,

Busquets²,

Escribá³

2016

Update on Dementia

Self Cite

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“…In a recent study Fiol-de Roque et al [66] have shown that (OHDHA) regulates membrane lipid composition and structure, cell signaling and, additionally, it improves cognitive scores in animal models of AD thereby representing a novel therapeutic candidate for the treatment of this disease.…”

Section: Aarti and Priyankamentioning

confidence: 99%

Review on Therapeutic Effects Mediated by Omega-3 Fatty Acids in Alzheimer’s Disease

Sati

Bhatt²

2018

Asian J Pharm Clin Res

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Alzheimer's disease (AD) is a neurodegenerative disorder with relevant unmet therapeutic needs. Both natural aging and AD have been associated with a significant decline in the Omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA), and accordingly, administration of DHA has been proposed as a possible treatment for this pathology. DHA and its derivatives like 2-hydroxy DHA-(OHDHA) have a strong therapeutic potential to treat AD. Studies have demonstrated that DHA induced lipid modifications are paralleled with a reduction in amyloid-beta (Αβ) accumulation and full recovery of cognitive impairment. Omega-3 fatty acids also caused alterations in the subcellular distribution of secretases and reduced Αβ-induced tau protein phosphorylation as well. Furthermore, OHDHA enhanced the survival of neuron-like differentiated cells exposed to different insults such as oligomeric Αβ and N-methyl-D-aspartate-mediated neurotoxicity. In conclusion, this review focuses on the pleiotropic effects of Omega-3 fatty acids that might prove beneficial to treat AD.

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“…Chairs: Graham Pawelec (Germany) and Doron Melamed (Israel). Session 5: Novel strategies for the treatment of neuro-and muscle-degeneration (Buga et al 2013;Phelps et al 2013;Fiol-deRoque et al 2013;Yeh et al 2013). Chairs: Jose Julio Rodrigez (Spain) and Abraham Reznick (Israel).…”

mentioning

confidence: 99%

Healthy ageing and regenerative medicine

Fraifeld

2013

Biogerontology

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Cognitive recovery and restoration of cell proliferation in the dentate gyrus in the 5XFAD transgenic mice model of Alzheimer’s disease following 2-hydroxy-DHA treatment

Cited by 48 publications

References 67 publications

Brain Lipids in the Pathophysiology and Treatment of Alzheimer’s Disease

Brain Lipids in the Pathophysiology and Treatment of Alzheimer’s Disease

Review on Therapeutic Effects Mediated by Omega-3 Fatty Acids in Alzheimer’s Disease

Healthy ageing and regenerative medicine

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