The level of 24-hydroxycholesteryl esters decreases in plasma of patients with Parkinson’s disease

Natale, Concetta Di; A, Monaco; Pedone, Carlo; Tessitore, Alessandro; Mase, Antonio De; Tedeschi, Gioacchino; Netti, Paolo A.; Abrescia, Paolo

doi:10.1016/j.neulet.2018.02.041

Cited by 25 publications

(17 citation statements)

References 37 publications

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“…Moreover, the sample size in the current study is much larger than the three previous studies, and our analyses also were controlled for potential confounders such as age, sex, smoking status, and statin use . Our study, consistent with Di Natale and colleagues, provides the most robust evidence to date supporting the hypothesis that higher levels of (S) 24‐OH‐cholesterol are inversely associated with PD.…”

Section: Discussionsupporting

confidence: 80%

“…There have been three previous studies investigating the relationship between (S) 24‐OH‐cholesterol levels and PD, each with fewer than 26 PD subjects. Lee and colleagues and Di Natale and colleagues reported lower plasma levels in PD compared to controls, whereas Björkhem and colleagues found no difference. The latter researchers suggested that the analysis in the Lee and colleagues study was confounded by the experimental choice of deuterated internal standard.…”

Section: Discussionmentioning

confidence: 95%

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Brain cholesterol metabolism and Parkinson's disease

Huang

Sterling

et al. 2019

Movement Disorders

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A BS TRACT: Background: Circulating cholesterol levels have been linked to PD, but not directly to brain physiology. Objective: To assess whether brain cholesterol metabolism is related to PD. Methods: Sixty PD patients and 64 controls were recruited from an academic movement disorder clinic (2009)(2010)(2011)(2012). Thirty-five PD patients and 33 controls returned approximately 36 months later. Fasting plasma (S)24-OH-cholesterol (brain-derived cholesterol metabolite) and 27-OH-cholesterol (peripheral cholesterol metabolite) were quantified. Odds ratios for PD were derived from logistic regression models, adjusting for potential confounders. Relationships between the oxysterols and clinical measurements were explored using Spearman correlation coefficients. Results: Mean age of PD subjects was 63.8 AE 8.3 years and disease duration was 5.0 AE 5.4 years. Plasma (S)24-OHcholesterol levels were inversely associated with the odds of having PD, with an odds ratio of 0.92 (95% confidence interval: 0.87-0.97) for each 1-ng/mL increase (P = 0.004).Compared to the lowest tertile, the odds ratio was 0.34 (0.12-0.98) for the second tertile (P = 0.045) and 0.08 (0.02-0.31) for the highest tertile (P < 0.001). Higher (S)24-OHcholesterol levels also were correlated with better sense of smell (r = 0.35; P = 0.01). No significant associations were found between clinical measures and 27-OH-cholesterol, a peripheral cholesterol metabolite. Furthermore, (S)24-OHcholesterol levels were stable over time, whereas 27-OHcholesterol decreased with time in both cases and controls. Conclusions: Results indicate that plasma (S)24-OHcholesterol (possibly reflecting brain cholesterol metabolism) is inversely linked to PD, is relatively stable over time, and may serve as a new biomarker for PD. Further investigation is necessary to determine the mechanistic and clinical implications.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 95%

Brain cholesterol metabolism and Parkinson's disease

Huang

Sterling

et al. 2019

Movement Disorders

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“…Good results with this technique have been achieved in neurological disorders (Garbayo et al 2012). It has been confirmed that in Parkinson disease (PD), neuron death is induced by oxidative stress as suggested by the increase in production of reactive oxygen species (ROS) and by the decreased activity of ROS-sensitive enzymes able to avoid the accumulation of neurotoxic compound into the brain such as lecithin-cholesterol acyltransferase (LCAT) (Di Natale et al 2018). Fernandez et al, treated PD-model animals with rasagiline mesylate (RM), a potent anti-oxidant molecules, encapsulated within PLGA microspheres.…”

Section: Single Emulsion Techniquementioning

confidence: 96%

Recent advances in the formulation of PLGA microparticles for controlled drug delivery

et al. 2020

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Polymeric microparticles (MPs) are recognized as very popular carriers to increase the bioavailability and bio-distribution of both lipophilic and hydrophilic drugs. Among different kinds of polymers, poly-(lactic-co-glycolic acid) (PLGA) is one of the most accepted materials for this purpose, because of its biodegradability (due to the presence of ester linkages that are degraded by hydrolysis in aqueous environments) and safety (PLGA is a Food and Drug Administration (FDA)-approved compound). Moreover, its biodegradability depends on the number of glycolide units present in the structure, indeed, lower glycol content results in an increased degradation time and conversely a higher monomer unit number results in a decreased time. Due to this feature, it is possible to design and fabricate MPs with a programmable and time-controlled drug release. Many approaches and procedures can be used to prepare MPs. The chosen fabrication methodology influences size, stability, entrapment efficiency, and MPs release kinetics. For example, lipophilic drugs as chemotherapeutic agents (doxorubicin), anti-inflammatory non-steroidal (indomethacin), and nutraceuticals (curcumin) were successfully encapsulated in MPs prepared by single emulsion technique, while water-soluble compounds, such as aptamer, peptides and proteins, involved the use of double emulsion systems to provide a hydrophilic compartment and prevent molecular degradation. The purpose of this review is to provide an overview about the preparation and characterization of drug-loaded PLGA MPs obtained by single, double emulsion and microfluidic techniques, and their current applications in the pharmaceutical industry. Graphic abstract

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“…The third study showed that plasma levels of esterified 24HC are significantly reduced in patients with PD and could reflect an impaired catalytic activity of LCAT as result of a higher level of oxidative stress in the CNS. Esterified 24HC in plasma was suggested to be a novel biomarker of neurodegeneration in PD as well as a measure of disease severity and progression [70]. In addition, several brain regions in patients with PD were characterized by a comprehensive lipidomics analysis: these were the primary visual cortex (a region that is mainly devoid of structural but not functional changes) and the amygdala and anterior cingulate cortex (two regions which contain Lewy bodies at the different disease stages but do not have such severe degeneration as the substantia nigra) [71].…”

Section: Cyp46a1 and Brain Cholesterol Levels In Ad Hd And Pdmentioning

confidence: 99%

Cholesterol 24-Hydroxylation by CYP46A1: Benefits of Modulation for Brain Diseases

Petrov

Pikuleva

2019

Neurotherapeutics

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Cholesterol 24-hydroxylation is the major mechanism for cholesterol removal from the brain and the reaction catalyzed by cytochrome P450 46A1 (CYP46A1), a CNS-specific enzyme. This review describes CYP46A1 in the context of cholesterol homeostasis in the brain and summarizes available experimental data on CYP46A1 association with different neurologic diseases, including the mechanisms by which changes in the CYP46A1 activity in the brain could be beneficial for these diseases. The modulation of CYP46A1 activity by genetic and pharmacologic means is also presented along with a brief synopsis of the two clinical trials that evaluate CYP46A1 as a therapeutic target for Alzheimer's disease as well as Dravet and Lennox-Gastaut syndromes.

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The level of 24-hydroxycholesteryl esters decreases in plasma of patients with Parkinson’s disease

Cited by 25 publications

References 37 publications

Brain cholesterol metabolism and Parkinson's disease

Brain cholesterol metabolism and Parkinson's disease

Recent advances in the formulation of PLGA microparticles for controlled drug delivery

Cholesterol 24-Hydroxylation by CYP46A1: Benefits of Modulation for Brain Diseases

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