Deutsch
 
Hilfe Datenschutzhinweis Impressum
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT
  Alpha-synuclein affects neurite morphology, autophagy, vesicle transport and axonal degeneration in CNS neurons.

Koch, J. C., Bitow, F., Haack, J., d'Hedouville, Z., Zhang, J. N., Tonges, L., et al. (2015). Alpha-synuclein affects neurite morphology, autophagy, vesicle transport and axonal degeneration in CNS neurons. Cell Death and Disease, 6: e1811. doi:10.1038/cddis.2015.169.

Item is

Dateien

einblenden: Dateien
ausblenden: Dateien
:
2181642.pdf (Verlagsversion), 4MB
Name:
2181642.pdf
Beschreibung:
-
OA-Status:
Sichtbarkeit:
Öffentlich
MIME-Typ / Prüfsumme:
application/pdf / [MD5]
Technische Metadaten:
Copyright Datum:
-
Copyright Info:
-
:
2181642_Suppl_1.jpg (Ergänzendes Material), 3MB
Name:
2181642_Suppl_1.jpg
Beschreibung:
-
OA-Status:
Sichtbarkeit:
Öffentlich
MIME-Typ / Prüfsumme:
image/jpeg / [MD5]
Technische Metadaten:
Copyright Datum:
-
Copyright Info:
-
Lizenz:
-
:
2181642_Suppl_2.jpg (Ergänzendes Material), 2MB
Name:
2181642_Suppl_2.jpg
Beschreibung:
-
OA-Status:
Sichtbarkeit:
Öffentlich
MIME-Typ / Prüfsumme:
image/jpeg / [MD5]
Technische Metadaten:
Copyright Datum:
-
Copyright Info:
-
Lizenz:
-
:
2181642_Suppl_3.jpg (Ergänzendes Material), 88KB
Name:
2181642_Suppl_3.jpg
Beschreibung:
-
OA-Status:
Sichtbarkeit:
Öffentlich
MIME-Typ / Prüfsumme:
image/jpeg / [MD5]
Technische Metadaten:
Copyright Datum:
-
Copyright Info:
-
Lizenz:
-

Externe Referenzen

einblenden:
ausblenden:
Beschreibung:
-
OA-Status:

Urheber

einblenden:
ausblenden:
 Urheber:
Koch, J. C., Autor
Bitow, F., Autor
Haack, J., Autor
d'Hedouville, Z., Autor
Zhang, J. N., Autor
Tonges, L., Autor
Michel, U., Autor
Oliveira, L. M. A., Autor
Jovin, T. M.1, Autor           
Liman, J., Autor
Tatenhorst, L., Autor
Bähr, M., Autor
Lingor, P., Autor
Affiliations:
1Emeritus Group Laboratory of Cellular Dynamics, MPI for Biophysical Chemistry, Max Planck Society, ou_578629              

Inhalt

einblenden:
ausblenden:
Schlagwörter: -
 Zusammenfassung: Many neuropathological and experimental studies suggest that the degeneration of dopaminergic terminals and axons precedes the demise of dopaminergic neurons in the substantia nigra, which finally results in the clinical symptoms of Parkinson disease (PD). The mechanisms underlying this early axonal degeneration are, however, still poorly understood. Here, we examined the effects of overexpression of human wildtype alpha-synuclein (alpha Syn-WT), a protein associated with PD, and its mutant variants alpha Syn-A30P and -A53T on neurite morphology and functional parameters in rat primary midbrain neurons (PMN). Moreover, axonal degeneration after overexpression of alpha Syn-WT and -A30P was analyzed by live imaging in the rat optic nerve in vivo. We found that overexpression of alpha Syn-WT and of its mutants A30P and A53T impaired neurite outgrowth of PMN and affected neurite branching assessed by Sholl analysis in a variant-dependent manner. Surprisingly, the number of primary neurites per neuron was increased in neurons transfected with alpha Syn. Axonal vesicle transport was examined by live imaging of PMN co-transfected with EGFP-labeled synaptophysin. Overexpression of all alpha Syn variants significantly decreased the number of motile vesicles and decelerated vesicle transport compared with control. Macroautophagic flux in PMN was enhanced by alpha Syn-WT and -A53T but not by alpha Syn-A30P. Correspondingly, colocalization of alpha Syn and the autophagy marker LC3 was reduced for alpha Syn-A30P compared with the other alpha Syn variants. The number of mitochondria colocalizing with LC3 as a marker for mitophagy did not differ among the groups. In the rat optic nerve, both alpha Syn-WT and -A30P accelerated kinetics of acute axonal degeneration following crush lesion as analyzed by in vivo live imaging. We conclude that alpha Syn overexpression impairs neurite outgrowth and augments axonal degeneration, whereas axonal vesicle transport and autophagy are severely altered.

Details

einblenden:
ausblenden:
Sprache(n): eng - English
 Datum: 2015-07-09
 Publikationsstatus: Online veröffentlicht
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1038/cddis.2015.169
 Art des Abschluß: -

Veranstaltung

einblenden:

Entscheidung

einblenden:

Projektinformation

einblenden:

Quelle 1

einblenden:
ausblenden:
Titel: Cell Death and Disease
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: -
Seiten: 12 Band / Heft: 6 Artikelnummer: e1811 Start- / Endseite: - Identifikator: -