Investigating the efficacy of a combination Aβ-targeted treatment in a mouse model of Alzheimer’s disease

Liu, Mingzhe; Jevtic, Stefan; Markham-Coultes, Kelly; Ellens, Nicholas; O’Reilly, Meaghan A.; Hynynen, Kullervo; Aubert, Isabelle; McLaurin, J.

doi:10.1016/j.brainres.2017.10.015

Cited by 29 publications

(19 citation statements)

References 46 publications

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“…In patient’s brain, there is an increased level of MI compared to healthy individuals, despite different pathogenesis of the disease, connected with the accumulation of neurotoxin-toxic amyloid A [86,87]. Liu et al [88] evaluated the brains of mice after 6 months of scyllo -inositol supplementation, observing the lower amyloid A content, the greater activity of microglia and the phagocytosis capacity compared to non-treated mice. Scyllo -inositol binds and stabilizes small soluble conformations of Aβ amyloid that are phagocytosed by microglia [88].…”

Section: Cyclitols For Nervous System Diseasesmentioning

confidence: 99%

“…Liu et al [88] evaluated the brains of mice after 6 months of scyllo -inositol supplementation, observing the lower amyloid A content, the greater activity of microglia and the phagocytosis capacity compared to non-treated mice. Scyllo -inositol binds and stabilizes small soluble conformations of Aβ amyloid that are phagocytosed by microglia [88].…”

Section: Cyclitols For Nervous System Diseasesmentioning

confidence: 99%

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The Healing-Promoting Properties of Selected Cyclitols—A Review

et al. 2018

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Introduction: Myo-inositol and its derivatives cyclitols play an important role in the processes of cell regulation, signal transduction, osmoregulation, and ion channel physiology, and are a component of the cell membrane. Free cyclitols present in food or released during the degradation of galactosyl cyclitols by bacteria (in digestive tract) show some physiological benefits. Aim: The aim of this paper is to present and analyze the documented data about curative and healing properties of cyclitols. Results and discussion: Cyclitols are well known compounds in the treatment of an accompanied diabetes insulin resistance, and also obesity and polycystic ovarian syndrome. d-chiro-Inositol deficiency exacerbates insulin resistance in the liver, muscles, and fat, while depletion of myo-inositol results in the development of diabetic complications. Cyclitols are successfully applied in treatment of polycystic ovarian syndrome, simultaneous are observed effective reducing of BMI, improving the hormonal profile, and increasing fertility. Moreover, cyclitols have anti-atherogenic, anti-oxidative, anti-inflammatory, and anti-cancer properties. Conclusion: The properties of cyclitols may be a good therapeutic option in the reduction of metabolically induced inflammation. Due to well drugs tolerance and low toxicity of these compounds, cyclitols are recommend for pregnant women and also for children. Another advantage is their widespread presence and easy availability, which encourages their use in medicine.

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Section: Cyclitols For Nervous System Diseasesmentioning

confidence: 99%

Section: Cyclitols For Nervous System Diseasesmentioning

confidence: 99%

The Healing-Promoting Properties of Selected Cyclitols—A Review

et al. 2018

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“…In the meantime, nine constituents were firstly characterized in rat brain (Supporting Information Table S1 marked # ) with the strategy mentioned above. According to the result, the compounds detected in rat brain are mainly small compounds of Poria and Acori Tatarinowii Rhizoma, which possibly attributed to the limited access of larger compounds to the brain due to the blood–brain barrier .…”

Section: Resultsmentioning

confidence: 99%

Development of a systematic strategy for the global identification and classification of the chemical constituents and metabolites of Kai‐Xin‐San based on liquid chromatography with quadrupole time‐of‐flight mass spectrometry combined with multiple data‐processing approaches

Wang

Liu

Yang

et al. 2018

J of Separation Science

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To rapidly identify and classify complicated components and metabolites for traditional Chinese medicines, a liquid chromatography with quadrupole time-of-flight mass spectrometry method combined with multiple data-processing approaches was established. In this process, Kai-Xin-San, a widely used classic traditional Chinese medicine preparation, was chosen as a model prescription. Initially, the fragmentation patterns, diagnostic product ions and neutral loss of each category of compounds were summarized by collision-induced dissociation analysis of representative standards. In vitro, the multiple product ions filtering technique was utilized to identify the chemical constituents for globally covering trace components. With this strategy, 108 constituents were identified, and compounds database was successfully established. In vivo, the prototype compounds were extracted based on the established database, and the neutral loss filtering technique combined with the drug metabolism reaction rules was employed to identify metabolites. Overall, 69 constituents including prototype and metabolites were characterized in rat plasma and nine constituents were firstly characterized in rat brain, which may be the potential active constituents resulting in curative effects by synergistic interaction. In conclusion, this study provides a generally applicable strategy to global metabolite identification for the complicated components in complex matrix and a chemical basis for further pharmacological research of Kai-Xin-San.

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“…Further, sI prevents tau hyperphosphorylation (Jin and Selkoe, 2015). These potentially beneficial effects have prompted development of sI and close sI analogs as potential treatments for AD/ADRD (Salloway et al, 2011;Morrone et al, 2016;Lee et al, 2017;Liu et al, 2018). A possible mechanism to explain the low sI signal in supraphysiologic-dose AAS users is that its synthetic enzyme, inositol epimerase, which converts myo-inositol to sI, may be inhibited by AAS.…”

Section: Supraphysiologic-dose Aas Exposures Are Associated With Neurmentioning

confidence: 99%

Supraphysiologic-dose anabolic–androgenic steroid use: A risk factor for dementia?

Kaufman

Kanayama

Hudson

et al. 2019

Neuroscience & Biobehavioral Reviews

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Supraphysiologic-dose anabolic-androgenic steroid (AAS) use is associated with physiologic, cognitive, and brain abnormalities similar to those found in people at risk for developing Alzheimer's Disease and its related dementias (AD/ADRD), which are associated with high brain β-amyloid (Aβ) and hyperphosphorylated tau (tau-P) protein levels. Supraphysiologic-dose AAS induces androgen abnormalities and excess oxidative stress, which have been linked to increased and decreased expression or activity of proteins that synthesize and eliminate, respectively, Aβ and tau-P. Aβ and tau-P accumulation may begin soon after initiating supraphysiologic-dose AAS use, which typically occurs in the early 20s, and their accumulation may be accelerated by other psychoactive substance use, which is common among non-medical AAS users. Accordingly, the widespread use of supraphysiologic-dose AAS may increase the numbers of people who develop dementia. Early diagnosis and correction of sex-steroid level abnormalities and excess oxidative stress could attenuate risk for developing AD/ADRD in supraphysiologic-dose AAS users, in people with other substance use disorders, and in people with low sex-steroid levels or excess oxidative stress associated with aging.

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Investigating the efficacy of a combination Aβ-targeted treatment in a mouse model of Alzheimer’s disease

Cited by 29 publications

References 46 publications

The Healing-Promoting Properties of Selected Cyclitols—A Review

The Healing-Promoting Properties of Selected Cyclitols—A Review

Development of a systematic strategy for the global identification and classification of the chemical constituents and metabolites of Kai‐Xin‐San based on liquid chromatography with quadrupole time‐of‐flight mass spectrometry combined with multiple data‐processing approaches

Supraphysiologic-dose anabolic–androgenic steroid use: A risk factor for dementia?

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