GM6 Attenuates Alzheimer’s Disease Pathology in APP Mice

Yu, Jin; Zhu, Hong; Taheri, Saeid; Mondy, William; Kirstein, Cheryl L.; Ko, Dorothy; Kindy, Mark S.

doi:10.1007/s12035-019-1517-2

Cited by 4 publications

(1 citation statement)

References 37 publications

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“…Experimental approaches have included both increasing and reducing of CAT‐B activity. Increasing of CAT‐B activity has been accomplished by overexpression of CAT‐B (Embury et al, 2017; Wang, Sun, et al, 2012), genetic ablation of cystatin C (Sun et al, 2008), deletion of cystatin B (which, like cystatin C, is an inhibitor of lysosomal cysteine proteases) (Yang et al, 2011), administration of a 6‐amino acid component of motoneuronotrophic factor, an endogenous neurotrophin (Yu et al, 2019), and feeding a phytonutrient‐enriched diet (Yu et al, 2020). Reducing of CAT‐B activity has been accomplished by administration of the selective cathepsin‐B inhibitor CA‐074 (Hook et al, 2008), knockout of CAT‐B (Hook et al, 2009), administration of the phosphodiesterase‐5 inhibitor Sildenafil (Orejana et al, 2015), treatment with bilobalide, a Ginkgo biloba extract (Shi et al, 2012), and treatment with E64d, a cysteine protease inhibitor of CAT‐B (Hook et al, 2014).…”

Section: Proteolytic Cleavage Of Aβmentioning

confidence: 99%

Experimental approaches for altering the expression of Abeta‐degrading enzymes

Loeffler

2023

Journal of Neurochemistry

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Cerebral clearance of amyloid β‐protein (Aβ) is decreased in early‐onset and late‐onset Alzheimer's disease (AD). Aβ is cleared from the brain by enzymatic degradation and by transport out of the brain. More than 20 Aβ‐degrading enzymes have been described. Increasing the degradation of Aβ offers an opportunity to decrease brain Aβ levels in AD patients. This review discusses the direct and indirect approaches which have been used in experimental systems to alter the expression and/or activity of Aβ‐degrading enzymes. Also discussed are the enzymes' regulatory mechanisms, the conformations of Aβ they degrade, where in the scheme of Aβ production, extracellular release, cellular uptake, and intracellular degradation they exert their activities, and changes in their expression and/or activity in AD and its animal models. Most of the experimental approaches require further confirmation. Based upon each enzyme's effects on Aβ (some of the enzymes also possess β‐secretase activity and may therefore promote Aβ production), its direction of change in AD and/or its animal models, and the Aβ conformation(s) it degrades, investigating the effects of increasing the expression of neprilysin in AD patients would be of particular interest. Increasing the expression of insulin‐degrading enzyme, endothelin‐converting enzyme‐1, endothelin‐converting enzyme‐2, tissue plasminogen activator, angiotensin‐converting enzyme, and presequence peptidase would also be of interest. Increasing matrix metalloproteinase‐2, matrix metalloproteinase‐9, cathepsin‐B, and cathepsin‐D expression would be problematic because of possible damage by the metalloproteinases to the blood brain barrier and the cathepsins' β‐secretase activity. Many interventions which increase the enzymatic degradation of Aβ have been shown to decrease AD‐type pathology in experimental models. If a safe approach can be found to increase the expression or activity of selected Aβ‐degrading enzymes in human subjects, then the possibility that this approach could slow the AD progression should be examined in clinical trials.

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Section: Proteolytic Cleavage Of Aβmentioning

confidence: 99%

Experimental approaches for altering the expression of Abeta‐degrading enzymes

Loeffler

2023

Journal of Neurochemistry

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Cyclooxygenase Succineptide Methyl Ester Combined with Calcium Blockers Inhibits Nlrp3 Inflammasome Activation and Alleviates the Lesions of Alzheimer's Disease Transgenic Mice

Meng,

Liu,

Zhang

et al. 2023

Preprint

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Plant-Based Nutritional Supplementation Attenuates LPS-Induced Low-Grade Systemic Activation

Zhu

Taheri

et al. 2021

IJMS

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Plant-based nutritional supplementation has been shown to attenuate and reduce mortality in the processes of both acute and chronic disorders, including diabetes, obesity, cardiovascular disease, cancer, inflammatory diseases, and neurological and neurodegenerative disorders. Low-level systemic inflammation is an important contributor to these afflictions and diets enriched in phytochemicals can slow the progression. The goal of this study was to determine the impact of lipopolysaccharide (LPS)-induced inflammation on changes in glucose and insulin tolerance, performance enhancement, levels of urinary neopterin and concentrations of neurotransmitters in the striatum in mouse models. Both acute and chronic injections of LPS (2 mg/kg or 0.33 mg/kg/day, respectively) reduced glucose and insulin tolerance and elevated neopterin levels, which are indicative of systemic inflammatory responses. In addition, there were significant decreases in striatal neurotransmitter levels (dopamine and DOPAC), while serotonin (5-HT) levels were essentially unchanged. LPS resulted in impaired execution in the incremental loading test, which was reversed in mice on a supplemental plant-based diet, improving their immune function and maintaining skeletal muscle mitochondrial activity. In conclusion, plant-based nutritional supplementation attenuated the metabolic changes elicited by LPS injections, causing systemic inflammatory activity that contributed to both systemic and neurological alterations.

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GM6 Attenuates Alzheimer’s Disease Pathology in APP Mice

Cited by 4 publications

References 37 publications

Experimental approaches for altering the expression of Abeta‐degrading enzymes

Experimental approaches for altering the expression of Abeta‐degrading enzymes

Cyclooxygenase Succineptide Methyl Ester Combined with Calcium Blockers Inhibits Nlrp3 Inflammasome Activation and Alleviates the Lesions of Alzheimer's Disease Transgenic Mice

Plant-Based Nutritional Supplementation Attenuates LPS-Induced Low-Grade Systemic Activation

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