![](http://investorshub.advfn.com/images/default_ih_profile2_4848.jpg?cb=0)
Monday, May 02, 2011 12:35:05 AM
Cell-Produced a-Synuclein Is Secreted in a Calcium-Dependent Manner by Exosomes and Impacts Neuronal Survival
Evangelia Emmanouilidou1,
Katerina Melachroinou1,
Theodoros Roumeliotis2,
Spiros D. Garbis2,
Maria Ntzouni3,
Lukas H. Margaritis3,
Leonidas Stefanis1,4, and
Kostas Vekrellis1
+ Author Affiliations
1Divisions of Basic Neurosciences and
2Biotechnology, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece,
3Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Athens 15701, Greece, and
4Second Department of Neurology, University of Athens Medical School, Athens 11527, Greece
Abstract
a-Synuclein is central in Parkinson's disease pathogenesis. Although initially a-synuclein was considered a purely intracellular protein, recent data suggest that it can be detected in the plasma and CSF of humans and in the culture media of neuronal cells. To address a role of secreted a-synuclein in neuronal homeostasis, we have generated wild-type a-synuclein and ß-galactosidase inducible SH-SY5Y cells. Soluble oligomeric and monomeric species of a-synuclein are readily detected in the conditioned media (CM) of these cells at concentrations similar to those observed in human CSF. We have found that, in this model, a-synuclein is secreted by externalized vesicles in a calcium-dependent manner. Electron microscopy and liquid chromatography–mass spectrometry proteomic analysis demonstrate that these vesicles have the characteristic hallmarks of exosomes, secreted intraluminar vesicles of multivesicular bodies. Application of CM containing secreted a-synuclein causes cell death of recipient neuronal cells, which can be reversed after a-synuclein immunodepletion from the CM. High- and low-molecular-weight a-synuclein species, isolated from this CM, significantly decrease cell viability. Importantly, treatment of the CM with oligomer-interfering compounds before application rescues the recipient neuronal cells from the observed toxicity. Our results show for the first time that cell-produced a-synuclein is secreted via an exosomal, calcium-dependent mechanism and suggest that a-synuclein secretion serves to amplify and propagate Parkinson's disease-related pathology.
Recent AEMD News
- Aethlon Medical Announces Financial Results for the Fiscal Year Ended March 31, 2024 and Provides Corporate Update • PR Newswire (US) • 06/27/2024 08:15:00 PM
- Aethlon Medical to Release Fiscal Year End Financial Results and Host Conference Call on June 27, 2024 • PR Newswire (US) • 06/21/2024 12:01:00 PM
- Aethlon Medical Receives Ethics Committee Approval for Hemopurifier® Cancer Trial • PR Newswire (US) • 06/18/2024 12:01:00 PM
- Aethlon Medical Prepares for Potentially Transformative Phase 1 Cancer Treatment Studies • PR Newswire (US) • 06/03/2024 12:01:00 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 05/24/2024 05:24:31 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 05/17/2024 08:05:28 PM
- Form EFFECT - Notice of Effectiveness • Edgar (US Regulatory) • 05/17/2024 04:15:21 AM
- Form 424B4 - Prospectus [Rule 424(b)(4)] • Edgar (US Regulatory) • 05/16/2024 08:05:23 PM
- Form POS AM - Post-Effective amendments for registration statement • Edgar (US Regulatory) • 05/15/2024 01:27:15 PM
- Aethlon Medical Announces Pricing of $4.7 Million Public Offering • PR Newswire (US) • 05/15/2024 01:15:00 PM
- Form S-1/A - General form for registration of securities under the Securities Act of 1933: [Amend] • Edgar (US Regulatory) • 05/13/2024 09:30:18 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 05/10/2024 12:01:40 PM
- Aethlon Medical Reports Positive Results From an In Vitro Binding Study of Its Hemopurifier® in Removing Extracellular Vesicles From Cancer Patient Plasma • PR Newswire (US) • 05/10/2024 12:01:00 PM
- Aethlon Medical Enters Into Materials Transfer Agreement for Santersus AG's NucleoCapture and HemoNucleoCapture Devices • PR Newswire (US) • 02/21/2024 01:01:00 PM
- Form 10-Q - Quarterly report [Sections 13 or 15(d)] • Edgar (US Regulatory) • 02/14/2024 10:15:40 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 02/14/2024 09:15:41 PM
- Aethlon Medical Announces Fiscal Third Quarter Financial Results and Provides Corporate Update • PR Newswire (US) • 02/14/2024 09:15:00 PM
- Aethlon Medical to Release Fiscal Third Quarter Financial Results and Host Conference Call on February 14, 2024 • PR Newswire (US) • 02/07/2024 01:00:00 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 01/02/2024 11:06:06 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 01/02/2024 11:04:32 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 01/02/2024 11:02:52 PM
- Form 8-K/A - Current report: [Amend] • Edgar (US Regulatory) • 12/22/2023 09:01:12 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 11/27/2023 12:49:31 PM
Glidelogic Corp. Becomes TikTok Shop Partner, Opening a New Chapter in E-commerce Services • GDLG • Jul 5, 2024 7:09 AM
Freedom Holdings Corporate Update; Announces Management Has Signed Letter of Intent • FHLD • Jul 3, 2024 9:00 AM
EWRC's 21 Moves Gaming Studios Moves to SONY Pictures Studios and Green Lights Development of a Third Upcoming Game • EWRC • Jul 2, 2024 8:00 AM
BNCM and DELEX Healthcare Group Announce Strategic Merger to Drive Expansion and Growth • BNCM • Jul 2, 2024 7:19 AM
NUBURU Announces Upcoming TV Interview Featuring CEO Brian Knaley on Fox Business, Bloomberg TV, and Newsmax TV as Sponsored Programming • BURU • Jul 1, 2024 1:57 PM
Mass Megawatts Announces $220,500 Debt Cancellation Agreement to Improve Financing and Sales of a New Product to be Announced on July 11 • MMMW • Jun 28, 2024 7:30 AM