scholarly journals Pharmacological inhibition of soluble epoxide hydrolase as a new therapy for Alzheimer’s Disease

2019 ◽  
Author(s):  
Christian Griñán-Ferré ◽  
Sandra Codony ◽  
Eugènia Pujol ◽  
Jun Yang ◽  
Rosana Leiva ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Therapeutic Effects ◽  
Beneficial Effects ◽  
Age Related ◽  
Novel Target ◽  
Age Related Cognitive Decline

AbstractThe inhibition of the enzyme soluble epoxide hydrolase (sEH) has demonstrated clinical therapeutic effects in several peripheral inflammatory-related diseases, with two compounds that have entered clinical trials. However, the role of this enzyme in the neuroinflammation process has been largely neglected. Herein, we disclose the pharmacological validation of sEH as a novel target for the treatment of Alzheimer’s Disease (AD). Of interest, we have found that sEH is upregulated in brains from AD patients. We have evaluated the cognitive impairment and the pathological hallmarks in two models of age-related cognitive decline and AD using three structurally different and potent sEH inhibitors as chemical probes. Our findings supported our expectations on the beneficial effects of central sEH inhibition, regarding of reducing cognitive impairment, tau hyperphosphorylation pathology and the number of amyloid plaques. Interestingly, our results suggest that reduction of inflammation in the brain is a relevant therapeutic strategy for all stages of AD.

Ginkgo biloba extract EGb 761® in the context of current developments in the diagnosis and treatment of age-related cognitive decline and Alzheimer's disease: a research perspective

2012 ◽  
Vol 24 (S1) ◽  
pp. S46-S50 ◽  
Author(s):  
Nicola T. Lautenschlager ◽  
Ralf Ihl ◽  
Walter E. Müller
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Ginkgo Biloba ◽  
Future Research ◽  
Egb 761 ◽  
Age Related ◽  
Age Related Cognitive Decline ◽  
Ageing Brain

ABSTRACTIn June 2011 a two-day expert meeting “The Ageing Brain” took place in Amsterdam, The Netherlands. The main aim was to discuss the available preclinical and clinical data on Ginkgo biloba special extract EGb 761® in the context of current developments in the diagnosis and treatment of age-related cognitive decline and Alzheimer's disease. 19 dementia experts covering the disciplines bio- and neurochemistry, gerontology, neurology, pharmacology, and psychiatry from Australia, Asia, Europe and North America reviewed available preclinical and clinical data for EGb 761® and identified core topics for future research. Based on a wide range of preclinical effects demonstrated for Ginkgo biloba, EGb 761® can be conceptualized as a multi-target compound with activity on distinct pathophysiological pathways in Alzheimer's disease (AD) and age-related cognitive decline. While symptomatic efficacy in dementia and mild cognitive impairment (MCI) has been demonstrated, interpretation of data from dementia prevention trials is complicated by important methodological issues. Bridging pre-clinical research and clinical research as well as deciding on suitable study designs for future trials with EGb 761® remain important questions. The participants of the “Ageing Brain” meeting on Ginkgo biloba special extract EGb 761® concluded that there is plenty of promising data, both pre-clinical and clinical, to consider future research with the compound targeting cognitive impairment in old age as a worthwhile activity.

scholarly journals Probiotics Fermentation Technology, a Novel Kefir Product, Ameliorates Cognitive Impairment in Streptozotocin-Induced Sporadic Alzheimer’s Disease in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Nesrine S. El Sayed ◽  
Esraa A. Kandil ◽  
Mamdooh H. Ghoneum
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Gut Microbiota ◽  
Neuronal Degeneration ◽  
Amyloid Plaque ◽  
Dependent Manner ◽  
Insulin Degrading Enzyme ◽  
Beneficial Effects ◽  
Fermentation Technology

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by cognitive impairment. Gut microbiota dysfunction (dysbiosis) is implicated in the pathology of AD and is associated with several detrimental consequences, including neurotransmitter depletion, oxidative stress, inflammation, apoptosis, and insulin resistance, which all contribute to the onset of AD. The objective of this study was to assess the effectiveness of Probiotics Fermentation Technology (PFT), a kefir product, in alleviating AD symptoms via regulation of the gut microbiota using a streptozotocin- (STZ-) induced AD mouse model and to compare its activity with simvastatin, which has been proven to effectively treat AD. Mice received one intracerebroventricular injection of STZ (3 mg/kg). PFT (100, 300, 600 mg/kg) and simvastatin (20 mg/kg) were administered orally for 3 weeks. PFT supplementation mitigated STZ-induced neuronal degeneration in the cortex and hippocampus, restored hippocampal acetylcholine levels, and improved cognition in a dose-dependent manner. These effects were accompanied by reductions in oxidative damage, proinflammatory cytokine expression, apoptosis, and tau hyperphosphorylation. Moreover, PFT hindered amyloid plaque accumulation via the enhancement of insulin-degrading enzyme. These beneficial effects were comparable to those produced by simvastatin. The results suggest that PFT can alleviate AD symptoms by regulating the gut microbiota and by inhibiting AD-related pathological events.

scholarly journals Calorie restriction slows age-related microbiota changes in an Alzheimer’s disease model in female mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Laura M. Cox ◽  
Marissa J. Schafer ◽  
Jiho Sohn ◽  
Julia Vincentini ◽  
Howard L. Weiner ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Intestinal Microbiota ◽  
Calorie Restriction ◽  
Disease Model ◽  
Tg2576 Mouse ◽  
Female Mice ◽  
Plaque Deposition ◽  
Age Related ◽  
Age Related Cognitive Decline

AbstractAlzheimer’s disease (AD) affects an estimated 5.8 million Americans, and advanced age is the greatest risk factor. AD patients have altered intestinal microbiota. Accordingly, depleting intestinal microbiota in AD animal models reduces amyloid-beta (Aβ) plaque deposition. Age-related changes in the microbiota contribute to immunologic and physiologic decline. Translationally relevant dietary manipulations may be an effective approach to slow microbiota changes during aging. We previously showed that calorie restriction (CR) reduced brain Aβ deposition in the well-established Tg2576 mouse model of AD. Presently, we investigated whether CR alters the microbiome during aging. We found that female Tg2576 mice have more substantial age-related microbiome changes compared to wildtype (WT) mice, including an increase in Bacteroides, which were normalized by CR. Specific gut microbiota changes were linked to Aβ levels, with greater effects in females than in males. In the gut, Tg2576 female mice had an enhanced intestinal inflammatory transcriptional profile, which was reversed by CR. Furthermore, we demonstrate that Bacteroides colonization exacerbates Aβ deposition, which may be a mechanism whereby the gut impacts AD pathogenesis. These results suggest that long-term CR may alter the gut environment and prevent the expansion of microbes that contribute to age-related cognitive decline.

scholarly journals Experimental Evidence of the Benefits of Acupuncture for Alzheimer's Disease: An Updated Review

2020 ◽  
Vol 14 ◽  
Author(s):  
Chao-Chao Yu ◽  
Yan-Jun Du ◽  
Shu-Qin Wang ◽  
Le-Bin Liu ◽  
Feng Shen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Apoptosis ◽  
Tau Phosphorylation ◽  
Therapeutic Effects ◽  
Beneficial Effects ◽  
Brain Responses ◽  
Growing Body ◽  
Neuron Function ◽  
Global Population

As the global population ages, the prevalence of Alzheimer's disease (AD), the most common form of dementia, is also increasing. At present, there are no widely recognized drugs able to ameliorate the cognitive dysfunction caused by AD. The failure of several promising clinical trials in recent years has highlighted the urgent need for novel strategies to both prevent and treat AD. Notably, a growing body of literature supports the efficacy of acupuncture for AD. In this review, we summarize the previously reported mechanisms of acupuncture's beneficial effects in AD, including the ability of acupuncture to modulate Aβ metabolism, tau phosphorylation, neurotransmitters, neurogenesis, synapse and neuron function, autophagy, neuronal apoptosis, neuroinflammation, cerebral glucose metabolism, and brain responses. Taken together, these findings suggest that acupuncture provides therapeutic effects for AD.

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