Disruption of neocortical histone H3 homeostasis by soluble Aβ: implications for Alzheimer's disease

Lithner, Christina Unger; Lacor, Pascale N.; Zhao, Wei; Mustafiz, Tamanna; Klein, William L.; Sweatt, J. David; Hernandez, Caterina M.

doi:10.1016/j.neurobiolaging.2012.12.028

Cited by 61 publications

(45 citation statements)

References 86 publications

(118 reference statements)

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“…Protein acetylation level is the result of the dynamic interplay of the activities of protein acetylases and deacetylases. In AD brains, the HDCA2 protein levels are increased (Graff et al, 2012) and the homeostasis of histone 3 acetylation is disrupted by soluble Aß (Lithner et al, 2013). Similar epigenetic alterations occurred in our untreated Tg mice, as shown by the increased HDCA2 protein levels and by the reduced level of histone 3 and 4 acetylation throughout the cortex and the hippocampus.…”

Section: Discussionsupporting

confidence: 78%

Oleuropein aglycone protects against pyroglutamylated-3 amyloid-ß toxicity: biochemical, epigenetic and functional correlates

Luccarini

Grossi

Rigacci

et al. 2015

Neurobiology of Aging

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a b s t r a c tAmyloid-ß (Aß) fragments, oligomeric Aß aggregates, and pyroglutamylated-Aß peptides, as well as epigenetic mechanisms and autophagy dysfunction all appear to contribute in various ways to Alzheimer's disease progression. We previously showed that dietary supplementation of oleuropein aglycone, a natural phenol abundant in the extra virgin olive oil, can be protective by reducing Aß42 deposits in the brain of young and middle-aged TgCRND8 mice. Here, we extended our study to aged TgCRND8 mice showing increased pE3-Aß in the brain deposits. We report that oleuropein aglycone is active against glutaminylcyclase-catalyzed pE3-Aß generation reducing enzyme expression and interferes both with Aß42 and pE3-Aß aggregation. Moreover, the phenol astonishingly activates neuronal autophagy even in mice at advanced stage of pathology, where it increases histone 3 and 4 acetylation, which matches both a decrease of histone deacetylase 2 expression and a significant improvement of synaptic function. The occurrence of these functional, epigenetic, and histopathologic beneficial effects even at a late stage of the pathology suggests that the phenol could be beneficial at the therapeutic, in addition to the prevention, level.

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Section: Discussionsupporting

confidence: 78%

Oleuropein aglycone protects against pyroglutamylated-3 amyloid-ß toxicity: biochemical, epigenetic and functional correlates

Luccarini

Grossi

Rigacci

et al. 2015

Neurobiology of Aging

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“…Recent data indicate that the protective effects of OLE in the diet of a Tg murine model of Aβ deposition could be traced bask, at least in part, to the increased acetylation of histone 3 and 4, that matched the reduced expression of HDAC-2 [40], whose levels are increased in the AD brain [285,286] and of glutaminyl cyclase (GC), the enzyme responsible for the generation of pE3Aβ, the most aggregating pyroglutamylated derivative of the Aβ 1-42 peptide in AD [287]. Interestingly, GC is significantly increased in the brain of AD patients [288].…”

Section: Histone Modificationsmentioning

confidence: 99%

Healthy Effects of Plant Polyphenols: Molecular Mechanisms

Leri

Scuto

Ontario

et al. 2020

IJMS

326

213

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The increasing extension in life expectancy of human beings in developed countries is accompanied by a progressively greater rate of degenerative diseases associated with lifestyle and aging, most of which are still waiting for effective, not merely symptomatic, therapies. Accordingly, at present, the recommendations aimed at reducing the prevalence of these conditions in the population are limited to a safer lifestyle including physical/mental exercise, a reduced caloric intake, and a proper diet in a convivial environment. The claimed health benefits of the Mediterranean and Asian diets have been confirmed in many clinical trials and epidemiological surveys. These diets are characterized by several features, including low meat consumption, the intake of oils instead of fats as lipid sources, moderate amounts of red wine, and significant amounts of fresh fruit and vegetables. In particular, the latter have attracted popular and scientific attention for their content, though in reduced amounts, of a number of molecules increasingly investigated for their healthy properties. Among the latter, plant polyphenols have raised remarkable interest in the scientific community; in fact, several clinical trials have confirmed that many health benefits of the Mediterranean/Asian diets can be traced back to the presence of significant amounts of these molecules, even though, in some cases, contradictory results have been reported, which highlights the need for further investigation. In light of the results of these trials, recent research has sought to provide information on the biochemical, molecular, epigenetic, and cell biology modifications by plant polyphenols in cell, organismal, animal, and human models of cancer, metabolic, and neurodegenerative pathologies, notably Alzheimer’s and Parkinson disease. The findings reported in the last decade are starting to help to decipher the complex relations between plant polyphenols and cell homeostatic systems including metabolic and redox equilibrium, proteostasis, and the inflammatory response, establishing an increasingly solid molecular basis for the healthy effects of these molecules. Taken together, the data currently available, though still incomplete, are providing a rationale for the possible use of natural polyphenols, or their molecular scaffolds, as nutraceuticals to contrast aging and to combat many associated pathologies.

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“…Upregulation of phosphorylation in H3 was also observed in the hippocampus of AD patients in some studies, but could not be confirmed by others (52, 53). Brain region-, gene-, or disease stage-specificity might affect epigenetic modification patterns.…”

Section: Epigenetic Changes In Aging-related Neurodegenerative Diseasesmentioning

confidence: 68%

“…Contrary to the general decrease in histone acetylation, histone methylation is reported to be upregulated in AD patients (52). Upregulation of phosphorylation in H3 was also observed in the hippocampus of AD patients in some studies, but could not be confirmed by others (52, 53).…”

Section: Epigenetic Changes In Aging-related Neurodegenerative Diseasesmentioning

confidence: 99%

Age-related epigenetic regulation in the brain and its role in neuronal diseases

Kim-Ha¹,

Kim²

2016

BMB Reports

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Accumulating evidence indicates many brain functions are mediated by epigenetic regulation of neural genes, and their dysregulations result in neuronal disorders. Experiences such as learning and recall, as well as physical exercise, induce neuronal activation through epigenetic modifications and by changing the noncoding RNA profiles. Animal models, brain samples from patients, and the development of diverse analytical methods have broadened our understanding of epigenetic regulation in the brain. Diverse and specific epigenetic changes are suggested to correlate with neuronal development, learning and memory, aging and age-related neuronal diseases. Although the results show some discrepancies, a careful comparison of the data (including methods, regions and conditions examined) would clarify the problems confronted in understanding epigenetic regulation in the brain.

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Disruption of neocortical histone H3 homeostasis by soluble Aβ: implications for Alzheimer's disease

Cited by 61 publications

References 86 publications

Oleuropein aglycone protects against pyroglutamylated-3 amyloid-ß toxicity: biochemical, epigenetic and functional correlates

Oleuropein aglycone protects against pyroglutamylated-3 amyloid-ß toxicity: biochemical, epigenetic and functional correlates

Healthy Effects of Plant Polyphenols: Molecular Mechanisms

Age-related epigenetic regulation in the brain and its role in neuronal diseases

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