Brain ageing and neurodegenerative disease: The role of cellular waste management

Daniele, Simona; Giacomelli, Chiara; Martini, Claudia

doi:10.1016/j.bcp.2018.10.030

Cited by 43 publications

(35 citation statements)

References 98 publications

(150 reference statements)

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“…Among the several factors involved, chronic and neuroinflammation, cellular senescence, genome instability and proteostasis dysregulation are listed [58,59]. Notably, even exogenous factors and toxins may increase the risk of neurodegenerative diseases onset by determining a persistent inflammatory status and oxidative stress [60,61]. Although different in clinical presentation, all these diseases share common features and mechanisms, including abnormal accumulation and aggregation of disease-specific proteins that lead to progressive loss of specific neurons and synapses in distinct brain regions [61,62].…”

Section: Polyphenol Effects On Neurocognitive Functionsmentioning

confidence: 99%

Polyphenol Health Effects on Cardiovascular and Neurodegenerative Disorders: A Review and Meta-Analysis

Potì

Santi

Spaggiari

et al. 2019

IJMS

197

127

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Several studies have demonstrated that polyphenol-enriched diets may have beneficial effects against the development of degenerative diseases, including atherosclerosis and disorders affecting the central nervous system. This activity has been associated not only with antioxidant and anti-inflammatory properties, but also with additional mechanisms, such as the modulation of lipid metabolism and gut microbiota function. However, long-term studies on humans provided controversial results, making the prediction of polyphenol impact on health uncertain. The aim of this review is to provide an overview and critical analysis of the literature related to the effects of the principal dietary polyphenols on cardiovascular and neurodegenerative disorders. We critically considered and meta-analyzed randomized controlled clinical trials involving subjects taking polyphenol-based supplements. Although some polyphenols might improve specific markers of cardiovascular risk and cognitive status, many inconsistent data are present in literature. Therefore, definitive recommendations for the use of these compounds in the prevention of cardiovascular disease and cognitive decline are currently not applicable. Once pivotal aspects for the definition of polyphenol bioactivity, such as the characterization of pharmacokinetics and safety, are addressed, it will be possible to have a clear picture of the realistic potential of polyphenols for disease prevention.

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Section: Polyphenol Effects On Neurocognitive Functionsmentioning

confidence: 99%

Polyphenol Health Effects on Cardiovascular and Neurodegenerative Disorders: A Review and Meta-Analysis

Potì

Santi

Spaggiari

et al. 2019

IJMS

197

127

View full text Add to dashboard Cite

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“…These neuronal diseases are chronic and progressive, decreasing the quality of life for both patients and their caregivers and bringing a heavy economic burden to society [2]. A small number of cases are caused by known genetic mutations, and studying these variants would help our understanding of the pathogenesis of these neurodegenerative disorders [3]. However, environmental factors, acting as susceptibility factors and/or triggers, play an important role in most cases [4].…”

Section: Introduction and Alcohol Use: Dual Effects And Mechanismsmentioning

confidence: 99%

Role of Alcohol Drinking in Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis

Peng

Yang²,

Joshi

et al. 2020

IJMS

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Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), increase as the population ages around the world. Environmental factors also play an important role in most cases. Alcohol consumption exists extensively and it acts as one of the environmental factors that promotes these neurodegenerative diseases. The brain is a major target for the actions of alcohol, and heavy alcohol consumption has long been associated with brain damage. Chronic alcohol intake leads to elevated glutamate-induced excitotoxicity, oxidative stress and permanent neuronal damage associated with malnutrition. The relationship and contributing mechanisms of alcohol with these three diseases are different. Epidemiological studies have reported a reduction in the prevalence of Alzheimer’s disease in individuals who drink low amounts of alcohol; low or moderate concentrations of ethanol protect against β-amyloid (Aβ) toxicity in hippocampal neurons; and excessive amounts of ethanol increase accumulation of Aβ and Tau phosphorylation. Alcohol has been suggested to be either protective of, or not associated with, PD. However, experimental animal studies indicate that chronic heavy alcohol consumption may have dopamine neurotoxic effects through the induction of Cytochrome P450 2E1 (CYP2E1) and an increase in the amount of α-Synuclein (αSYN) relevant to PD. The findings on the association between alcohol consumption and ALS are inconsistent; a recent population-based study suggests that alcohol drinking seems to not influence the risk of developing ALS. Additional research is needed to clarify the potential etiological involvement of alcohol intake in causing or resulting in major neurodegenerative diseases, which will eventually lead to potential therapeutics against these alcoholic neurodegenerative diseases.

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“…Accumulating evidence indicates that neuroin ammatory and neurodegenerative processes are triggered by the dysfunction of the UPS [11,66]. In particular, decreased levels and transcriptional activity of the nuclear factor Nrf2 contributes to propagate oxidative stress and neurodegeneration-related proteins [12].…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein E polymorphism and oxidative stress in human peripheral blood cells: can physical activity reactivate the proteasome system through epigenetic mechanisms?

Piccarducci

Daniele

Polini

et al. 2020

Preprint

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Background Alzheimer’s Disease (AD) is characterised by proteasome activity impairment and oxidative stress, resulting in β-amyloid (Aβ) production/degradation imbalance. Apolipoprotein E (ApoE) is implicated in Aβ clearance, and ApoE ε4 isoform predisposes to AD development. Regular physical activity is known to reduce AD progression. However, the impact of ApoE polymorphism and physical exercise on Aβ production and proteasome system activity has never been investigated in human peripheral blood cells.Methods Healthy subjects were enrolled and classified based on the ApoE polymorphism (by the restriction fragment length polymorphism technique) and physical activity level (Borg Scale), dividing them in ApoE ε4/non-ε4 carriers and active/non-active subjects. The plasma antioxidant capability (AOC), the erythrocyte Aβ production/accumulation, and the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated proteasome functionality were evaluated in all groups by chromatographic and immunoenzymatic assay, respectively. Moreover, epigenetic mechanisms were investigated considering the expression of the histone deacetylase 6, employing a competitive ELISA, and the modulation of two keys miRNAs (miR-153-3p and miR-195-5p), through miRNeasy Serum/Plasma Mini Kit.Results ApoE ε4 subjects showed a reduction in plasma AOC and an increase of the Nrf2 blocker, miR-153-3p, contributing to an enhancement of the erythrocyte concentration of Aβ. Physical exercise increased plasma AOC and reduced the amount of Aβ and its precursor, involving a reduced miR-153-3p expression and a miR-195-5p enhancement.Conclusions Our data highlight the impact of ApoE genotype on the amyloidogenic pathway and the proteasome system, and suggest the positive impact of physical exercise, also through epigenetic mechanisms.

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Brain ageing and neurodegenerative disease: The role of cellular waste management

Cited by 43 publications

References 98 publications

Polyphenol Health Effects on Cardiovascular and Neurodegenerative Disorders: A Review and Meta-Analysis

Polyphenol Health Effects on Cardiovascular and Neurodegenerative Disorders: A Review and Meta-Analysis

Role of Alcohol Drinking in Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis

Apolipoprotein E polymorphism and oxidative stress in human peripheral blood cells: can physical activity reactivate the proteasome system through epigenetic mechanisms?

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