Amyloid-beta-induced neurotoxicity is reduced by inhibition of glycogen synthase kinase-3

Koh, Seong‐Ho; Noh, Min Young; Kim, Seung Hyun

doi:10.1016/j.brainres.2007.10.064

Cited by 113 publications

(96 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In animal models, overactive GSK3B has been associated with memory impairment [34] . The phosphorylation of GSK3B at Serine 9 leads to its inactivation [35,36] , which may prevent Tau hyperphosphorylation and also have potential neuroprotective effects against Aβ toxicity [37,39] . GSK3B is also expressed in human platelets in higher amounts than in other blood cells.…”

Section: Glycogen Synthase Kinase and Taumentioning

confidence: 99%

Platelet biomarkers in Alzheimer’s disease

Talib

Joaquim²,

Forlenza³

2012

WJP

View full text Add to dashboard Cite

The search for diagnostic and prognostic markers in Alzheimer's disease (AD) has been an area of active research in the last decades. Biochemical markers are correlates of intracerebral changes that can be identified in biological fluids, namely: peripheral blood (total blood, red and white blood cells, platelets, plasma and serum), saliva, urine and cerebrospinal fluid. An important feature of a biomarker is that it can be measured objectively and evaluated as (1) an indicator of disease mechanisms (markers of core pathogenic processes or the expression of downstream effects of these processes), or (2) biochemical responses to pharmacological or therapeutic intervention, which can be indicative of disease modification. Platelets have been used in neuropharmacological models since the mid-fifties, as they share several homeostatic functions with neurons, such as accumulation and release of neurotransmitters, responsiveness to variations in calcium concentration, and expression of membrane-bound compounds. Recent studies have shown that platelets also express several components related to the pathogenesis of AD, in particular to the amyloid cascade and the regulation of oxidative stress: thus they can be used in the search for biomarkers of the disease process. For instance, platelets are the most important source of circulating forms of the amyloid precursor protein and other important proteins such as Tau and glycogen synthase kinase-3B. Moreover, platelets express enzymes involved in membrane homeostasis (e.g., phospholipase A2), and markers of the inflammatory process and oxidative stress. In this review we summarize the available literature and discuss evidence concerning the potential use of platelet markers in AD.

show abstract

Section: Glycogen Synthase Kinase and Taumentioning

confidence: 99%

Platelet biomarkers in Alzheimer’s disease

Talib

Joaquim²,

Forlenza³

2012

WJP

View full text Add to dashboard Cite

show abstract

“…These studies suggested that enhanced GSK-3 signalling is responsible for excessive amyloid peptide production that is followed by neurotoxcity. Accordingly, inhibition of GSK-3 reduces amyloid-peptide induced neurotoxcity in cultured neurons (57).…”

Section: Gsk-3 and Amyloid Peptidesmentioning

confidence: 99%

GSK‐3: A key player in neurodegeneration and memory

Giese

2009

IUBMB Life

124

View full text Add to dashboard Cite

Abnormalities in molecular signalling have been implicated in neurodegeneration. It is emerging that glycogen synthase kinase‐3 (GSK‐3) is a key signalling molecule that induces neurodegeneration and deficits in memory formation related to Alzheimer's disease (AD). Early stages of AD are associated with deficits in memory formation before neuronal cell death is detectable. Recent studies in rodents have suggested that these impairments in memory formation might result from increased GSK‐3 signalling, because enhanced GSK‐3 activity impairs hippocampal memory formation. GSK‐3 activity blocks synaptic long‐term potentiation and induces long‐term depression. Furthermore, increased GSK‐3 signalling is likely to be a key contributor to the formation of the pathological hallmarks in AD, neurofibrillary tangles (NFTs) and amyloid plaques. Recent studies with mouse models have indicated that GSK‐3, but not cyclin‐dependent kinase 5, is critical for hyperphosphorylation of the cytoskeletal protein tau, which is the prerequisite for NFT formation in AD. Furthermore, increased GSK‐3 signalling in AD mice causes abnormal processing of the amyloid precursor protein so that amyloid peptide production augments and neurotoxicity is induced. Taken together, the current evidences suggest that increased GSK‐3 signalling may be responsible for the deficits in memory formation in early stages of AD and neurodegeneration in later stages of the disease. © 2009 IUBMB IUBMB Life 61(5): 516–521, 2009

show abstract

“…aβ significantly increases roS production and enhances membrane lipid peroxidation, leading to neuronal apoptosis. it has been demonstrated that antioxidants have a beneficial effect in Aβ-induced neurotoxicity (20) and neurodegenerative disorders (21,22). Therefore, in ad, antioxidant therapies may delay the occurrence of apoptosis or prevent it altogether.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rb1 protects PC12 cells against β-amyloid-induced cell injury

Xie

Wang²,

Li³

et al. 2010

Mol Med Rep

View full text Add to dashboard Cite

Abstract. excessive accumulation of β-amyloid (aβ) has been proposed as a pivotal event in the pathogenesis of alzheimer's disease. Possible mechanisms underlying aβ-induced neuronal cytotoxicity include oxidative stress and apoptosis. reactive oxygen species (roS) have been proposed to be involved in the apoptotic mechanism of aβ-induced cytotoxicity. Ginsenoside rb1 (Grb1), which is among the key compounds of ginsenoside, found in ginseng, may be a potent scavenger of roS. To examine the potential protective effect of Grb1 in aβ 25-35 -induced cytotoxicity, cells were pre-treated with Grb1 for 24 h, and then aβ [25][26][27][28][29][30][31][32][33][34][35] was added to the medium for an additional 24 h. exposure to aβ led to the accumulation of roS and lipid peroxidation, eventually causing a decrease in the Bcl-2/ Bax ratio, caspase-3 activation, cell apoptosis and cell death. Pre-treatment with Grb1 not only inhibited aβ-induced roS overproduction and lipid peroxidation, but also increased the Bcl-2/Bax ratio and attenuated caspase-3 activation, thereby improving cell survival. Grb1 may therefore act as a roS scavenger, and such antioxidant properties may play a protective role against aβ-induced cell injury. Further exploration of Grb1 antioxidant properties may provide novel therapeutic strategies for the treatment of alzheimer's disease.

show abstract

Amyloid-beta-induced neurotoxicity is reduced by inhibition of glycogen synthase kinase-3

Cited by 113 publications

References 32 publications

Platelet biomarkers in Alzheimer’s disease

Platelet biomarkers in Alzheimer’s disease

GSK‐3: A key player in neurodegeneration and memory

Ginsenoside Rb1 protects PC12 cells against β-amyloid-induced cell injury

Contact Info

Product

Resources

About