- Case Report of a 63-Year-Old Patient With Alzheimer Disease and a Novel Presenilin 2 Mutation. [Journal Article]
- ADAlzheimer Dis Assoc Disord 2018 Aug 16
- Sesamin and sesamolin reduce amyloid-β toxicity in a transgenic Caenorhabditis elegans. [Journal Article]
- BPBiomed Pharmacother 2018 Aug 14; 107:656-664
- Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by β-amyloid (Aβ) plaques in the brain. At the present, there is no approved drug with a proven disease-modifying eff...
Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by β-amyloid (Aβ) plaques in the brain. At the present, there is no approved drug with a proven disease-modifying effect. Sesame seed (Sesame indicum) has long been known as a healthy food in Southeast Asian countries. Sesame lignans obtained from sesame seed possess antioxidant property that exhibit a variety of beneficial effects in various models. The objective of this study was to investigate the protective effects of sesame lignans including sesamin, sesamolin, and sesamol against Aβ toxicity in Caenorhabditis elegans (C. elegans) model of Aβ toxicity and to address whether these sesame lignans have a positive effect on lifespan extension. A transgenic C. elegans expressing human Aβ was used to investigate protective effects of sesame lignans against Aβ toxicity. Sesamin and sesamolin significantly alleviated Aβ-induced paralysis. The real-time PCR revealed that both sesamin and sesamolin did not affect the expression of Aβ transgene. However, we found that only sesamin inhibited Aβ oligomerization. These findings demonstrated that, among three sesame lignans tested, sesamin protected against Aβ toxicity by reducing toxic Aβ oligomers. Sesamin and sesamolin also significantly improved Aβ-induced defect in chemotaxis behavior and reversed the defect to normal. Moreover, sesamin prolonged median and mean lifespan of the wild type worm. On the other hand, sesamolin and sesamol failed to extend lifespan. These results offer valuable evidence for the future use of sesamin in the development of agents for the treatment of AD. It is also worth investigating the structure-activity relationship of lignan-related structures and their anti-Aβ toxicity activities in the future.
- Phloroglucinol ameliorates cognitive impairments by reducing the amyloid β peptide burden and pro-inflammatory cytokines in the hippocampus of 5XFAD mice. [Journal Article]
- FRFree Radic Biol Med 2018 Aug 14
- Among the various causative factors involved in the pathogenesis of Alzheimer's disease (AD), oxidative stress has emerged as an important factor. Phloroglucinol is a polyphenol component of phlorota...
Among the various causative factors involved in the pathogenesis of Alzheimer's disease (AD), oxidative stress has emerged as an important factor. Phloroglucinol is a polyphenol component of phlorotannin, which is found at sufficient levels in Ecklonia cava (E. cava). Phloroglucinol has been reported to exert antioxidant activities in various tissues. Previously, we reported that the stereotaxic injection of phloroglucinol regulated synaptic plasticity in an AD mouse model. In this study, we aimed to investigate the effects of oral administration of phloroglucinol in AD. The oral administration of phloroglucinol for 2 months attenuated the impairments in cognitive function observed in 6-month-old 5X familial AD (5XFAD) mice, as assessed with the T-maze and Y-maze tests. The administration of phloroglucinol for 2 months in 5XFAD mice caused a reduction in the number of amyloid plaques and in the protein level of BACE1, a major amyloid precursor protein cleavage enzyme, together with γ-secretase. Phloroglucinol also restored the reduction in dendritic spine density and the number of mature spines in the hippocampi of 5XFAD mice. In addition, phloroglucinol-administered 5XFAD mice displayed lower protein levels of GFAP and Iba-1 and mRNA levels of TNF-α and IL-6 compared with vehicle-administered 5XFAD mice. These results demonstrated that phloroglucinol alleviated the neuropathological features and behavioral phenotypes in the 5XFAD mouse model. Taken together, our results suggest that phloroglucinol has therapeutic potential for AD treatment.
- 7.0 tesla high resolution MRI study on intracerebral migration of magnet-labeled neural stem cells in a mouse model of Alzheimer's disease. [Journal Article]
- MRMagn Reson Imaging 2018 Aug 14
- CONCLUSIONS: NSCs underwent diffuse and non-directional migration to the surroundings after they were transplanted to the hippocampus of APP/PS1 transgenic AD mice, and this migration pattern could be traced in vivo by MRI when they were labeled with magnet.
- The opioid system in stress-induced memory disorders: From basic mechanisms to clinical implications in posttraumatic stress disorder and Alzheimer's disease. [Review]
- PNProg Neuropsychopharmacol Biol Psychiatry 2018 Aug 14
- Cognitive and emotional impairment are a serious consequence of stress exposure and are core features of neurological and psychiatric conditions that involve memory disorders. Indeed, acute and chron...
Cognitive and emotional impairment are a serious consequence of stress exposure and are core features of neurological and psychiatric conditions that involve memory disorders. Indeed, acute and chronic stress are high-risk factors for the onset of posttraumatic stress disorder (PTSD) and Alzheimer's disease (AD), two devastating brain disorders associated with memory dysfunction. Besides the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis, stress response also involves the activation of the opioid system in brain regions associated with stress regulation and memory processing. In this context, it is possible that stress-induced memory disorders may be attributed to alterations in the interaction between the neuroendocrine stress system and the opioid system. In this review, we: (1) describe the effects of acute and chronic stress on memory, and the modulatory role of the opioid system, (2) discuss the contribution of the opioid system to the pathophysiology of PTSD and AD, and (3) present evidence of current and potential therapies that target the opioid receptors to treat PTSD- and AD-associated symptoms.
- Neuroprotective effects of bergenin in Alzheimer's disease: Investigation through molecular docking, in vitro and in vivo studies. [Journal Article]
- BBBehav Brain Res 2018 Aug 14
- Alzheimer's disease (AD) is an enervating and chronic progressive neurodegenerative disorder, occurring frequently in the elderly and adversely affecting intellectual capabilities and the cognitive p...
Alzheimer's disease (AD) is an enervating and chronic progressive neurodegenerative disorder, occurring frequently in the elderly and adversely affecting intellectual capabilities and the cognitive processes. Bergenin possesses efficacious antioxidant, antiulcerogenic, anti-HIV, hepatoprotective, neuroprotective, anti-inflammatory and immunomodulatory activity along with antinociceptive effect and wound healing properties. Previous studies have shown that bergenin has in vitro bovine adrenal tyrosine hydroxylase inhibitory activity, mushroom tyrosinase inhibitory activities, β-secretase (BACE-1) enzyme inhibitory activity and prevented neuronal death in the primary culture of rat cortical neurons. Protein tyrosine phosphatase-1B (PTP1B) is an intriguing target for anticancer and antidiabetic drugs and has recently been implicated to act as a positive regulator of neuroinflammation. Bergenin is also found to inhibit human protein tyrosine phosphatase-1B (hPTP1B) in vitro. Thus, bergenin was screened by molecular docking study using GOLD suite (version 5.2), CCDC for predicting its activity against targets of AD management like acetylcholinesterase (AChE) (1B41), butyrylcholinesterase (BuChE) (1P0I), Tau protein kinase 1 (GSK-3β) (1J1B), BACE-1 (1FKN) wherein the GOLD score and fitness of bergenin were comparable to those of standard drugs like donepezil, galanthamine, physostigmine, etc. Bergenin demonstrated dose-dependent inhibition of both AChE and BuChE in vitro and found to be safe up to 50 µM when screened in vitro on SH-SY5Y cell lines by cytotoxicity studies using MTT and Alamar blue assays. It also led to dose-dependent prevention of NMDA induced toxicity in these cells. Pretreatment with bergenin (14 days) in rats at three dose levels (20, 40 and 80 mg/kg; p.o.) significantly (p < 0.01) and dose-dependently alleviated amnesia induced by scopolamine (2 mg/kg, i.p.). The therapeutic effect of bergenin supplementation for 28 days, at three dose levels, was also evaluated in streptozotocin (3 mg/kg, ICV, unilateral) induced AD model in Wistar rats using Morris water maze and Y maze on 7th, 14th, 21st and 28th days. STZ caused significant (p < 0.001) cognitive impairment and cholinergic deficit and increased oxidative stress in rats. Bergenin could significantly ameliorate STZ induced behavioral deficits, inhibit the AChE and BuChE activity in parallel with an increase in the diminished GSH levels in a dose-dependent fashion. The histopathological investigations were also supportive of this datum. The bergenin treatment at 80 mg/kg led to significant (p < 0.05) abatement of the raised Aβ-1-42 levels and alleviated the perturbed p- tau levels leading to significantly low (p < 0.01) levels of p-tau in brain homogenates of rats as compared to ICV STZ injected rats. In conclusion, the observed effects might be attributed to the cholinesterase inhibitory activity of bergenin coupled with its antioxidant effect, anti-inflammatory activity and reduction of Aβ-1-42 and p-tau levels which could have collectively helped in the attenuation of cognitive deficits. The current findings of the study are indicative of the promising preventive and ameliorative potential of bergenin in the management of AD through multiple targets.
- Circulating APP, NCAM and Aβ serve as biomarkers for Alzheimer's disease. [Journal Article]
- BRBrain Res 2018 Aug 14
- Alzheimer's disease (AD) is the most common neurodegenerative disease and the early diagnosis and intervention are important for valid treatment of AD. However, there are few biomarkers for the diagn...
Alzheimer's disease (AD) is the most common neurodegenerative disease and the early diagnosis and intervention are important for valid treatment of AD. However, there are few biomarkers for the diagnosis and monitoring of AD. In the present study, circulating APP, NCAM, Aβ40, and Aβ42 were measured in order to identify which marker or combination of markers could be useful, cost-effective and noninvasive biomarkers for diagnosing and continuously monitoring AD. The results showed that circulating APP, NCAM, Aβ40, and Aβ42 were different between the AD group and the control group. Importantly, the combination of the four biomarkers had the highest AUC (0.997) with the highest sensitivity (98.5). Therefore, circulating APP, NCAM, Aβ40, and Aβ42 can be used as desirable biomarkers for AD diagnosis and monitoring.
- Go with the flow - microfluidics approaches for amyloids research. [Journal Article]
- CAChem Asian J 2018 Aug 17
- The rapid development of cost-efficient microfluidic devices has received tremendous attention from scientists of diverse fields. The growing potential of utilizing microfluidic platforms has further...
The rapid development of cost-efficient microfluidic devices has received tremendous attention from scientists of diverse fields. The growing potential of utilizing microfluidic platforms has further advanced the ability to integrate existing technology into microfluidic devices. Thus, allowing scientists to approach questions in fundamental fields, such as amyloid research, using new and otherwise unachievable conditions. Amyloids are associated with neurodegeneration and are in the forefront of many research efforts worldwide. The newly emerged microfluidic technology can serve as a novel research tool providing a platform for developing new methods in this field. In this review, we summarize the recent progress in amyloids research using microfluidic approaches. These approaches are driven from various fields, including physical chemistry, electrochemistry, biochemistry, and cell biology. Moreover, the new insights into novel microfluidic approaches for amyloid research reviewed here can be easily modified for other research interests.
- Plasma adiponectin array in women with Alzheimer's disease. [Journal Article]
- EPEndokrynol Pol 2018 Aug 17
- Introduction Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. Typical features of AD include memory loss, social dysfunction and physical impairment. Although the...
Introduction Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. Typical features of AD include memory loss, social dysfunction and physical impairment. Although the pathological findings in the central nervous system are well established, the etiological factors are poorly known. Recent studies suggested the role of metabolic disturbances in the development of AD neurodegeneration. Adiponectin, an anti-inflammatory and metabolism regulating factor, was linked to AD. Aim The aim was to examine whether adiponectin fractions combined with insulin/insulin resistance-associated metabolic parameters correlate with AD progression. Material and methods The study comprised 98 women: 27 with moderate to severe AD, 31 with AD at early stage and 40 healthy controls, matched for age and BMI. To evaluate memory impairment, the MMSE was performed. Plasma total adiponectin and its high-, medium- and low molecular weights were measured with ELISA. Anthropometric, clinical and metabolic parameters were assessed. Correlations between adiponectin array and measured parameters were evaluated. Results In comparison to the controls, enhanced levels of total and medium molecular weight adiponectin characterized AD individuals. In AD, we found correlations between adiponectin array, and anthropometric and biochemical parameters. After adjustment to BMI, a significant increase of the total adiponectin and high- and medium molecular weight fractions was observed. A negative correlation between low molecular weight adiponectin and MMSE was found. Conclusions Our results indicate a possible link between adiponectin variations and AD. We hypothesize that changes in adiponectin profile observed in AD result from compensatory mechanism against neuropathological processes, as well as from adiponectin homeostasis impairment.
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- Hypertension, diabetes and neurodegenerative diseases: is there a clinical link through the Ca2+/cAMP signalling interaction? [Journal Article]
- CHCurr Hypertens Rev 2018 Aug 16
- CONCLUSIONS: Considering the discovery of our group entitled "calcium paradox" due to Ca2+/cAMP signalling interaction, in this review I discussed the virtual involvement of this interaction in the pleiotropic effects of CCBs, including the possible role of the Ca2+/cAMP signalling interaction in the association between hypertension and higher risk for the decline of cognition, and diabetes.