Human astrocytes transfer aggregated alpha-synuclein via tunneling nanotubes

Rostami, Jinar (author): Uppsala universitet,Uppsala University,Geriatrik,Institutionen för medicinsk cellbiologi,Molekylär geriatrik/Rudbäcklaboratoriet

Holmqvist, Staffan (author): Lund University,Lunds universitet,Stamcellslaboratoriet för sjukdomsmodellering i det centrala nervsystemet,Forskargrupper vid Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,IPSC Laboratory for CNS Disease Modeling,Lund University Research Groups,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Lund Univ, Wallenberg Neurosci Ctr, Stem Cell Lab CNS Dis Modeling, Dept Expt Med Sci, S-22184 Lund, Sweden.;Lund Univ, Strateg Res Area MultiPk, S-22184 Lund, Sweden.;Lund Univ, Lund Stem Cell Ctr, S-22184 Lund, Sweden.

Lindström, Veronica (author): Uppsala universitet,Uppsala University,Geriatrik,Molekylär geriatrik/Rudbäcklaboratoriet

Westermark, Gunilla (author): Uppsala universitet,Uppsala University,Institutionen för medicinsk cellbiologi

Ingelsson, Martin (author): Uppsala universitet,Uppsala University,Geriatrik,Molekylär geriatrik/Rudbäcklaboratoriet

Bergström, Joakim (author): Uppsala universitet,Uppsala University,Geriatrik,Molekylär geriatrik/Rudbäcklaboratoriet

Roybon, Laurent (author): Lund University,Lunds universitet,Stamcellslaboratoriet för sjukdomsmodellering i det centrala nervsystemet,Forskargrupper vid Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,IPSC Laboratory for CNS Disease Modeling,Lund University Research Groups,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Lund Univ, Wallenberg Neurosci Ctr, Stem Cell Lab CNS Dis Modeling, Dept Expt Med Sci, S-22184 Lund, Sweden.;Lund Univ, Strateg Res Area MultiPk, S-22184 Lund, Sweden.;Lund Univ, Lund Stem Cell Ctr, S-22184 Lund, Sweden.

Erlandsson, Anna (author): Uppsala universitet,Uppsala University,Geriatrik,Molekylär geriatrik/Rudbäcklaboratoriet

(creator_code:org_t)

SOC NEUROSCIENCE, 2017
2017
English 19 s.
In: The Journal of Neuroscience. - : SOC NEUROSCIENCE. - 0270-6474 .- 1529-2401. ; 37:49, s. 11835-11853

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Abstract Subject headings

Many lines of evidence suggest that the Parkinson’s disease (PD)-related protein α-synuclein (α-SYN) can propagate from cell to cell in a prion-like manner. However, the cellular mechanisms behind the spreading remain elusive. Here, we show that human astrocytes derived from embryonic stem cells actively transfer aggregated α-SYN to nearby astrocytes via direct contact and tunneling nanotubes (TNTs). Failure in the astrocytes’ lysosomal digestion of excess α-SYN oligomers results in α-SYN deposits in the trans-Golgi network followed by endoplasmic reticulum swelling and mitochondrial disturbances. The stressed astrocytes respond by conspicuously sending out TNTs, enabling intercellular transfer of α-SYN to healthy astrocytes, which in return deliver mitochondria, indicating a TNT-mediated rescue mechanism. Using a pharmacological approach to inhibit TNT formation, we abolished the transfer of both α-SYN and mitochondria. Together, our results highlight the role of astrocytes in α-SYN cell-to-cell transfer, identifying possible pathophysiological events in the PD brain that could be of therapeutic relevance.

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)

By the author/editor: Rostami, Jinar; Holmqvist, Staff ...; Lindström, Veron ...; Sigvardson, Jess ...; Westermark, Guni ...; Ingelsson, Marti ...; show more...; Bergström, Joaki ...; Roybon, Laurent; Erlandsson, Anna; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Neurology

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