scholarly journals Icariin Prevents Amyloid Beta-Induced Apoptosis via the PI3K/Akt Pathway in PC-12 Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Dongdong Zhang ◽  
Zhe Wang ◽  
Chenxia Sheng ◽  
Weijun Peng ◽  
Shan Hui ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pc12 Cells ◽  
Amyloid Beta ◽  
Chinese Herb ◽  
Protective Effects ◽  
Amyloid Beta Protein ◽  
Neuroprotective Effects ◽  
Pi3k Inhibitor Ly294002 ◽  
Induced Apoptosis

Icariin is a prenylated flavonol glycoside derived from the Chinese herbEpimedium sagittatumthat exerts a variety of pharmacological activities and shows promise in the treatment and prevention of Alzheimer’s disease. In this study, we investigated the neuroprotective effects of icariin against amyloid beta protein fragment 25–35 (Aβ25–35) induced neurotoxicity in cultured rat pheochromocytoma PC12 cells and explored potential underlying mechanisms. Our results showed that icariin dose-dependently increased cell viability and decreasedAβ25–35-induced apoptosis, as assessed by MTT assay and Annexin V/propidium iodide staining, respectively. Results of western blot analysis revealed that the selective phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 suppressed icariin-induced Akt phosphorylation, suggesting that the protective effects of icariin are associated with activation of the PI3K/Akt signaling pathway. LY294002 also blocked the icariin-induced downregulation of proapoptotic factors Bax and caspase-3 and upregulation of antiapoptotic factor Bcl-2 inAβ25–35-treated PC12 cells. These findings provide further evidence for the clinical efficacy of icariin in the treatment of Alzheimer’s disease.

Proteolytic processing of the amyloid-beta protein precursor of Alzheimer's disease

2002 ◽  
Vol 38 ◽  
pp. 37-49 ◽  
Author(s):  
Janelle Nunan ◽  
David H Small
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Alternative Pathway ◽  
Protein A ◽  
Proteolytic Processing ◽  
Gamma Secretase ◽  
Amyloid Beta Protein ◽  
Protein Precursor ◽  
Amyloid Beta Protein Precursor

The proteolytic processing of the amyloid-beta protein precursor plays a key role in the development of Alzheimer's disease. Cleavage of the amyloid-beta protein precursor may occur via two pathways, both of which involve the action of proteases called secretases. One pathway, involving beta- and gamma-secretase, liberates amyloid-beta protein, a protein associated with the neurodegeneration seen in Alzheimer's disease. The alternative pathway, involving alpha-secretase, precludes amyloid-beta protein formation. In this review, we describe the progress that has been made in identifying the secretases and their potential as therapeutic targets in the treatment or prevention of Alzheimer's disease.

scholarly journals Classic Prescription, Kai-Xin-San, Ameliorates Alzheimer’s Disease as an Effective Multitarget Treatment: From Neurotransmitter to Protein Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Sirui Guo ◽  
Jiahong Wang ◽  
Huarong Xu ◽  
Weiwei Rong ◽  
Cheng Gao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pc12 Cells ◽  
Protein Signaling ◽  
Pi3k Inhibitor Ly294002 ◽  
Single Target ◽  
Biological Methods ◽  
Cognition Impairment ◽  
First Time

Alzheimer’s disease (AD) is a widespread neurodegenerative disease caused by complicated disease-causing factors. Unsatisfactorily, curative effects of approved anti-AD drugs were not good enough due to their actions on single-target, which led to desperate requirements for more effective drug therapies involved in multiple pathomechanisms of AD. The anti-AD effect with multiple action targets of Kai-Xin-San (KXS), a classic prescription initially recorded in Bei Ji Qian Jin Yao Fang and applied in the treatment of dementia for thousands of years, was deciphered with modern biological methods in our study. Aβ25-35 and D-gal-induced AD rats and Aβ25-35-induced PC12 cells were applied to establish AD models. KXS could significantly improve cognition impairment by decreasing neurotransmitter loss and enhancing the expression of PI3K/Akt. For the first time, KXS was confirmed to improve the expression of PI3K/Akt by neurotransmitter 5-HT. Thereinto, PI3K/Akt could further inhibit Tau hyperphosphorylation as well as the apoptosis induced by oxidative stress and neuroinflammation. Moreover, all above-mentioned effects were verified and blocked by PI3K inhibitor, LY294002, in Aβ25-35-induced PC12 cells, suggesting the precise regulative role of KXS in the PI3K/Akt pathway. The utilization and mechanism elaboration of KXS have been proposed and dissected in the combination of animal, molecular, and protein strategies. Our results demonstrated that KXS could ameliorate AD by regulating neurotransmitter and PI3K/Akt signal pathway as an effective multitarget treatment so that the potential value of this classic prescription could be explored from a novel perspective.

scholarly journals Increased Cerebrospinal Fluid Production as a Possible Mechanism Underlying Caffeine's Protective Effect against Alzheimer's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Peter Wostyn ◽  
Debby Van Dam ◽  
Kurt Audenaert ◽  
Peter Paul De Deyn
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Late Onset ◽  
Senile Plaques ◽  
Protective Effects ◽  
Caffeine Consumption ◽  
Neuroprotective Effects ◽  
Csf Production

Alzheimer's disease (AD), the most common type of dementia among older people, is characterized by the accumulation of β-amyloid (Aβ) senile plaques and neurofibrillary tangles composed of hyperphosphorylated tau in the brain. Despite major advances in understanding the molecular etiology of the disease, progress in the clinical treatment of AD patients has been extremely limited. Therefore, new and more effective therapeutic approaches are needed. Accumulating evidence from human and animal studies suggests that the long-term consumption of caffeine, the most commonly used psychoactive drug in the world, may be protective against AD. The mechanisms underlying the suggested beneficial effect of caffeine against AD remain to be elucidated. In recent studies, several potential neuroprotective effects of caffeine have been proposed. Interestingly, a recent study in rats showed that the long-term consumption of caffeine increased cerebrospinal fluid (CSF) production, associated with the increased expression of Na+-K+ATPase and increased cerebral blood flow. Compromised function of the choroid plexus and defective CSF production and turnover, with diminished clearance of Aβ, may be one mechanism implicated in the pathogenesis of late-onset AD. If reduced CSF turnover is a risk factor for AD, then therapeutic strategies to improve CSF flow are reasonable. In this paper, we hypothesize that long-term caffeine consumption could exert protective effects against AD at least in part by facilitating CSF production, turnover, and clearance. Further, we propose a preclinical experimental design allowing evaluation of this hypothesis.

1,8-Cineole (Eucalyptol) Mitigates Inflammation in Amyloid Beta Toxicated PC12 Cells: Relevance to Alzheimer’s Disease

2013 ◽  
Vol 39 (2) ◽  
pp. 344-352 ◽  
Author(s):  
Andleeb Khan ◽  
Kumar Vaibhav ◽  
Hayate Javed ◽  
Rizwana Tabassum ◽  
Md. Ejaz Ahmed ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pc12 Cells ◽  
Amyloid Beta

Lipophilic ferulic acid derivatives protect PC12 cells against oxidative damage via modulating β-amyloid aggregation and activating Nrf2 enzymes

2020 ◽  
Vol 11 (5) ◽  
pp. 4707-4718 ◽  
Author(s):  
Yu Wu ◽  
Yu-gang Shi ◽  
Xiao-liang Zheng ◽  
Ya-li Dang ◽  
Chen-min Zhu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Oxidative Damage ◽  
Ferulic Acid ◽  
Pc12 Cells ◽  
Amyloid Beta ◽  
Neuroprotective Effect ◽  
Amyloid Aggregation ◽  
Β Amyloid

Ferulic acid (FA) has been shown to have a neuroprotective effect on Alzheimer's disease induced by amyloid-beta (Aβ) neurotoxicity.

scholarly journals Polyphenols in Alzheimer’s Disease and in the Gut–Brain Axis

2020 ◽  
Vol 8 (2) ◽  
pp. 199 ◽  
Author(s):  
V. Prakash Reddy ◽  
Puspa Aryal ◽  
Sara Robinson ◽  
Raheemat Rafiu ◽  
Mark Obrenovich ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Polyphenolic Compounds ◽  
Brain Barrier ◽  
Bacterial Metabolism ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Bacterial Metabolites ◽  
Blood Brain

Polyphenolic antioxidants, including dietary plant lignans, modulate the gut–brain axis, which involves transformation of these polyphenolic compounds into physiologically active and neuroprotector compounds (called human lignans) through gut bacterial metabolism. These gut bacterial metabolites exert their neuroprotective effects in various neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and also have protective effects against other diseases, such as cardiovascular diseases, cancer, and diabetes. For example, enterolactone and enterodiol, the therapeutically relevant polyphenols, are formed as the secondary gut bacterial metabolites of lignans, the non-flavonoid polyphenolic compounds found in plant-based foods. These compounds are also acetylcholinesterase inhibitors, and thereby have potential applications as therapeutics in AD and other neurological diseases. Polyphenols are also advanced glycation end product (AGE) inhibitors (antiglycating agents), and thereby exert neuroprotective effects in cases of AD. Thus, gut bacterial metabolism of lignans and other dietary polyphenolic compounds results in the formation of neuroprotective polyphenols—some of which have enhanced blood–brain barrier permeability. It is hypothesized that gut bacterial metabolism-derived polyphenols, when combined with the nanoparticle-based blood–brain barrier (BBB)-targeted drug delivery, may prove to be effective therapeutics for various neurological disorders, including traumatic brain injury (TBI), AD, and PD. This mini-review addresses the role of polyphenolic compounds in the gut–brain axis, focusing on AD.

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