Brain metabolism and Alzheimer's disease: The prospect of a metabolite-based therapy

Thomas, Sean C.; Alhasawi, Azhar; Auger, Christopher; Appanna, Vasu D.

doi:10.1007/s12603-014-0511-7

Cited by 41 publications

(25 citation statements)

References 64 publications

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“…Interestingly, in a study examining the effects of metal in the diet, retinal Aβ abundance was found to increase dramatically in an aluminum-fed 5xFAD mouse [154]. The potential involvement of metal in AD has been reported before [37, 172]. In two other studies using the 5xFAD mouse, retinal Aβ 40 and Aβ 42 elevation were reported, with notable detection in the RPE [148, 150].…”

Section: Ad-specific Ocular Pathology In Animal Modelsmentioning

confidence: 85%

Ocular indicators of Alzheimer’s: exploring disease in the retina

et al. 2016

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Although historically perceived as a disorder confined to the brain, our understanding of Alzheimer’s disease (AD) has expanded to include extra-cerebral manifestation, with mounting evidence of abnormalities in the eye. Among ocular tissues, the retina, a developmental outgrowth of the brain, is marked by an array of pathologies in patients suffering from AD, including nerve fiber layer thinning, degeneration of retinal ganglion cells, and changes to vascular parameters. While the hallmark pathological signs of AD, amyloid β-protein (Aβ) plaques and neurofibrillary tangles (NFT) comprising hyperphosphorylated tau (pTau) protein, have long been described in the brain, identification of these characteristic biomarkers in the retina has only recently been reported. In particular, Aβ deposits were discovered in post-mortem retinas of advanced and early stage cases of AD, in stark contrast to non-AD controls. Subsequent studies have reported elevated Aβ42/40 peptides, morphologically diverse Aβ plaques, and pTau in the retina. In line with the above findings, animal model studies have reported retinal Aβ deposits and tauopathy, often correlated with local inflammation, retinal ganglion cell degeneration, and functional deficits. This review highlights the converging evidence that AD manifests in the eye, especially in the retina, which can be imaged directly and non-invasively. Visual dysfunction in AD patients, traditionally attributed to well-documented cerebral pathology, can now be reexamined as a direct outcome of retinal abnormalities. As we continue to study the disease in the brain, the emerging field of ocular AD warrants further investigation of how the retina may faithfully reflect the neurological disease. Indeed, detection of retinal AD pathology, particularly the early presenting amyloid biomarkers, using advanced high-resolution imaging techniques may allow large-scale screening and monitoring of at-risk populations.

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Section: Ad-specific Ocular Pathology In Animal Modelsmentioning

confidence: 85%

Ocular indicators of Alzheimer’s: exploring disease in the retina

et al. 2016

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“…Another emerging natural role of Aβ is in immune defense [664] [665], which partly relates to the inflammatory pathways briefly discussed in this review. In combination with molecules that target the energy crisis and mitochondrial disease of AD [161,[666][667][668][669] and distinct metal regulatory pathways [670], there are many promising directions to future therapies in AD that should replace the amyloid-alone strategies as a main priority in efforts to tackle this dreadful disease.…”

Section: Multifunctional Natural Compounds Against Admentioning

confidence: 99%

Alzheimer’s disease: How metal ions define β-amyloid function

Kepp

2017

Coordination Chemistry Reviews

136

139

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“…These abnormal situations have to be neutralized or at least mitigated if a living system is to survive. The very fact of consuming O 2 is rife with hazards as this process is inherently associated with oxidative stress [1][2][3]. The reducing factors such as NADH and FADH 2 resulting from the metabolism of a carbon source is oxidized in order to create a proton gradient and a membrane potential, the underlying power behind the synthesis of ATP, the universal energy currency in all cells.…”

Section: Introductionmentioning

confidence: 99%

Metabolic manipulation by Pseudomonas fluorescens: a powerful stratagem against oxidative and metal stress

MacLean

Bley

Appanna

2020

Journal of Medical Microbiology

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Metabolism is the foundation of all living organisms and is at the core of numerous if not all biological processes. The ability of an organism to modulate its metabolism is a central characteristic needed to proliferate, to be dormant and to survive any assault. Pseudomonas fluorescens is bestowed with a uniquely versatile metabolic framework that enables the microbe to adapt to a wide range of conditions including disparate nutrients and toxins. In this mini-review we elaborate on the various metabolic reconfigurations evoked by this microbial system to combat reactive oxygen/nitrogen species and metal stress. The fine-tuning of the NADH/NADPH homeostasis coupled with the production of α-keto-acids and ATP allows for the maintenance of a reductive intracellular milieu. The metabolic networks propelling the synthesis of metabolites like oxalate and aspartate are critical to keep toxic metals at bay. The biochemical processes resulting from these defensive mechanisms provide molecular clues to thwart infectious microbes and reveal elegant pathways to generate value-added products.

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Brain metabolism and Alzheimer's disease: The prospect of a metabolite-based therapy

Cited by 41 publications

References 64 publications

Ocular indicators of Alzheimer’s: exploring disease in the retina

Ocular indicators of Alzheimer’s: exploring disease in the retina

Alzheimer’s disease: How metal ions define β-amyloid function

Metabolic manipulation by Pseudomonas fluorescens: a powerful stratagem against oxidative and metal stress

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