NIH PubMed latest 20 articles on Alzheimer's amyloid

Galantamine inhibits calpain-calcineurin signaling activated by beta-amyloid in human neuroblastoma SH-SY5Y cells.

Li Q, Fang J, Yang M, Wu D, Zhang L, Zhang Y

Galantamine inhibits calpain-calcineurin signaling activated by beta-amyloid in human neuroblastoma SH-SY5Y cells.

Neurosci Lett. 2010 Aug 23;480(3):173-7

Authors: Li Q, Fang J, Yang M, Wu D, Zhang L, Zhang Y

Galantamine, which is currently used in the treatment of patients with Alzheimer's disease (AD), has been shown to have a neuroprotective effect against beta-amyloid (Abeta) peptide-induced toxicity, which is involved in the pathogenesis of AD. In this study, we investigated the mechanism underlying the protective effect of galantamine on Abeta-induced toxicity in human neuroblastoma cells (SH-SY5Y). Using MTT and LDH leakage assays, we observed that galantamine pretreatment significantly prevented Abeta1-40-induced cell death. Abeta1-40-induced overexpression and increased cleavage of both calpain and calcineurin were observed by Western blotting and double immunofluorescent staining. Increased calcineurin phosphatase activity and decreased level of pSer112 BAD were also observed in Abeta1-40-damaged cells. However, all these alterations were found to be reversed by galantamine pretreatment. We also found that the neuroprotection of galantamine can be blocked by an alpha7 nAChR antagonist. Overall, our results suggest that galantamine may prevent the neuronal damage induced by Abeta1-40 through a mechanism related to the regulation of calpain-calcineurin activation and BAD phosphorylation, which may involve the participation of alpha7 nAChR.

PMID: 20665950 [PubMed - in process]

Prion protein and Abeta-related synaptic toxicity impairment.

Prion protein and Abeta-related synaptic toxicity impairment.

EMBO Mol Med. 2010 Jul 21;

Authors: Calella AM, Farinelli M, Nuvolone M, Mirante O, Moos R, Falsig J, Mansuy IM, Aguzzi A

Alzheimer's disease (AD), the most common neurodegenerative disorder, goes along with extracellular amyloid-beta (Abeta) deposits. The cognitive decline observed during AD progression correlates with damaged spines, dendrites and synapses in hippocampus and cortex. Numerous studies have shown that Abeta oligomers, both synthetic and derived from cultures and AD brains, potently impair synaptic structure and functions. The cellular prion protein (PrP(C)) was proposed to mediate this effect. We report that ablation or overexpression of PrP(C) had no effect on the impairment of hippocampal synaptic plasticity in a transgenic model of AD. These findings challenge the role of PrP(C) as a mediator of Abeta toxicity.See accompanying article: http://dx.doi.org/10.1002/emmm.201000088.

PMID: 20665634 [PubMed - as supplied by publisher]

Sporadic inclusion body myositis: possible pathogenesis inferred from biomarkers.

Weihl CC, Pestronk A

Sporadic inclusion body myositis: possible pathogenesis inferred from biomarkers.

Curr Opin Neurol. 2010 Jul 20;

Authors: Weihl CC, Pestronk A

PURPOSE OF REVIEW: The relevance of proteins that accumulate and aggregate in the muscle fibers of patients with sporadic inclusion body myositis (sIBM) is unknown. Many of these proteins also aggregate in other disorders, including Alzheimer's disease, leading to speculation that sIBM pathogenesis has similarities to neurodegenerative disorders. Our review will discuss current studies on these protein biomarkers and their utility in sIBM diagnosis. RECENT FINDINGS: Two 'classical' components of sIBM aggregates (amyloid beta and phospho-tau) have been re-evaluated. Three additional components of aggregates (TDP-43, p62, and LC3) have been identified. The sensitivity and specificity of these biomarkers has been explored. Two studies suggest that TDP-43 may have clinical utility in distinguishing sIBM from other inflammatory myopathies. SUMMARY: The fact that sIBM muscle accumulates multiple protein aggregates with no single protein appearing in every sIBM patient biopsy suggests that it is not presently possible to place pathogenic blame on any single protein (i.e. amyloid beta or TDP-43). Instead changes in protein homeostasis may lead to the accumulation of different proteins that have a propensity to aggregate in skeletal muscle. Therapies aimed at improving protein homeostasis, instead of targeting a specific protein that may or may not accumulate in all sIBM patients, could be useful future strategies for this devastating and enigmatic disorder.

PMID: 20664349 [PubMed - as supplied by publisher]

Indoleamine 2,3-dioxygenase and 3-hydroxykynurenine modifications are found in the neuropathology of Alzheimer's disease.

Indoleamine 2,3-dioxygenase and 3-hydroxykynurenine modifications are found in the neuropathology of Alzheimer's disease.

Redox Rep. 2010;15(4):161-8

Authors: Bonda DJ, Mailankot M, Stone JG, Garrett MR, Staniszewska M, Castellani RJ, Siedlak SL, Zhu X, Lee HG, Perry G, Nagaraj RH, Smith MA

Tryptophan metabolism, through the kynurenine pathway, produces neurotoxic intermediates that are implicated in the pathogenesis of Alzheimer's disease. In particular, oxidative stress via 3-hydroxykynurenine (3-HK) and its cleaved product 3-hydroxyanthranilic acid (3-HAA) significantly damages neuronal tissue and may potentially contribute to a cycle of neurodegeneration through consequent amyloid-beta accumulation, glial activation, and up-regulation of the kynurenine pathway. To determine the role of the kynurenine pathway in eliciting and continuing oxidative stress within Alzheimer's diseased brains, we used immunocytochemical methods to show elevated levels of 3-HK modifications and the upstream, rate-limiting enzyme indoleamine 2,3-dioxygenase (IDO-1) in Alzheimer's diseased brains when compared to controls. Importantly, the association of IDO-1 with senile plaques was confirmed and, for the first time, IDO-1 was shown to be specifically localized in conjunction with neurofibrillary tangles. As senile plaques and neurofibrillary tangles are the pathological hallmarks of Alzheimer's disease, our study provides further evidence that the kynurenine pathway is involved with the destructive neurodegenerative pathway of Alzheimer's disease.

PMID: 20663292 [PubMed - in process]

Two functions, one molecule: a metal-binding and a targeting moiety to combat Alzheimer's disease.

Hureau C, Sasaki I, Gras E, Faller P

Two functions, one molecule: a metal-binding and a targeting moiety to combat Alzheimer's disease.

Chembiochem. 2010 May 3;11(7):950-3

Authors: Hureau C, Sasaki I, Gras E, Faller P

PMID: 20401891 [PubMed - indexed for MEDLINE]