| Title |
Effect of α-Synuclein on Amyloid β-Induced Toxicity: Relevance to Lewy Body Variant of Alzheimer Disease
|
|---|---|
| Published in |
Neurochemical Research, February 2013
|
| DOI | 10.1007/s11064-013-0982-7 |
| Pubmed ID | |
| Authors |
Rosa Resende, Sueli C. F. Marques, Elisabete Ferreiro, Isaura Simões, Catarina R. Oliveira, Cláudia M. F. Pereira |
| Abstract |
Alzheimer's disease, the most prevalent age-related neurodegenerative disease, is characterized by the presence of extracellular senile plaques composed of amyloid-beta (Aβ) peptide and intracellular neurofibrillary tangles. More than 50 % of Alzheimer's disease (AD) patients also exhibit abundant accumulation of α-synuclein (α-Syn)-positive Lewy bodies. This Lewy body variant of AD (LBV-AD) is associated with accelerated cognitive dysfunction and progresses more rapidly than pure AD. In addition, it has been suggested that Aβ and α-Syn can directly interact. In this study we investigated the effect of α-Syn on Aβ-induced toxicity in cortical neurons. In order to mimic the intracellular accumulation of α-Syn observed in the brain of LBV-AD patients, we used valproic acid (VPA) to increase its endogenous expression levels. The release of α-Syn from damaged presynaptic terminals that occurs during the course of the disease was simulated by challenging cells with recombinant α-Syn. Our results showed that either VPA-induced α-Syn upregulation or addition of recombinant α-Syn protect primary cortical neurons from soluble Aβ1-42 decreasing the caspase-3-mediated cell death. It was also found that neuroprotection against Aβ-induced toxicity mediated by α-Syn overexpression involves the PI3K/Akt cell survival pathway. Furthermore, recombinant α-Syn was shown to directly interact with Aβ1-42 and to decrease the levels of Aβ1-42 oligomers, which might explain its neuroprotective effect. In conclusion, we demonstrate that either endogenous or exogenous α-Syn can be neuroprotective against Aβ-induced cell death, suggesting a cell defence mechanism during the initial stages of the mixed pathology. |
Mendeley readers
The data shown below were compiled from readership statistics for 49 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Portugal | 1 | 2% |
| Unknown | 48 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 13 | 27% |
| Researcher | 7 | 14% |
| Student > Bachelor | 5 | 10% |
| Professor | 4 | 8% |
| Student > Master | 4 | 8% |
| Other | 8 | 16% |
| Unknown | 8 | 16% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 19 | 39% |
| Medicine and Dentistry | 6 | 12% |
| Neuroscience | 6 | 12% |
| Biochemistry, Genetics and Molecular Biology | 4 | 8% |
| Chemistry | 2 | 4% |
| Other | 1 | 2% |
| Unknown | 11 | 22% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 February 2013.
All research outputs
#20,184,694
of 22,699,621 outputs
Outputs from Neurochemical Research
#1,686
of 2,086 outputs
Outputs of similar age
#249,700
of 282,983 outputs
Outputs of similar age from Neurochemical Research
#20
of 24 outputs
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