Alteration of Mitochondrial Integrity as Upstream Event in the Pathophysiology of SOD1-ALS

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Search: WFRF:(Wegner L.) > (2020-2022) > Alteration of Mitoc...

1 of 2
Previous record
Next record
To hitlist

Alteration of Mitochondrial Integrity as Upstream Event in the Pathophysiology of SOD1-ALS

Günther, René (author): Department of Neurology, University Hospital Carl Gustav Carus Dresden, Technical University Dresden, Dresden, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Dresden, Germany

Pal, Arun (author): Department of Neurology, University Hospital Carl Gustav Carus Dresden, Technical University Dresden, Dresden, Germany; Dresden High Magnetic Field Laboratory (HLD), Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany

Williams, Chloe (author): Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB)

Zimyanin, Vitaly L. (author): Department of Neurology, University Hospital Carl Gustav Carus Dresden, Technical University Dresden, Dresden, Germany; Department of Molecular Physiology and Biological Physics, University of Virginia, VA, Charlottesville, United States

Liehr, Maria (author): Department of Neurology, University Hospital Carl Gustav Carus Dresden, Technical University Dresden, Dresden, Germany

von Neubeck, Cläre (author): German Cancer Consortium(DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), Heidelberg, Germany; OncoRay—National Center for Radiation Research in Oncology, University Hospital Carl Gustav Carus Dresden, Technical University Dresden, Dresden, Germany; Clinic for Particle Therapy, West German Proton Therapy Centre Essen (WPE) gGmbH, University Medical Centre of Essen, Essen, Germany

Krause, Mechthild (author): German Cancer Consortium(DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), Heidelberg, Germany; OncoRay—National Center for Radiation Research in Oncology, University Hospital Carl Gustav Carus Dresden, Technical University Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden—Rossendorf, Institute of Radiooncology—OncoRay, Dresden, Germany; Department of Radiotherapy and Radiation Oncology, University Hospital Carl Gustav Carus Dresden, Technical University Dresden, Dresden, Germany; National Center for Tumor Diseases (NCT), Partner Site Dresden, University Hospital Carl Gustav Carus Dresden, Technical University Dresden, Dresden, Germany

Parab, Mrudula G. (author): Department of Neurology, University Hospital Carl Gustav Carus Dresden, Technical University Dresden, Dresden, Germany

Petri, Susanne (author): Department of Neurology, Hannover Medical School, Hannover, Germany

Kalmbach, Norman (author): Department of Neurology, Hannover Medical School, Hannover, Germany

Marklund, Stefan L. (author): Umeå universitet,Klinisk kemi

Sterneckert, Jared (author): Center for Regenerative Therapies Dresden, Technical University Dresden, Dresden, Germany

Andersen, Peter M., 1962- (author): Umeå universitet,Neurovetenskaper

Wegner, Florian (author): Department of Neurology, Hannover Medical School, Hannover, Germany

Gilthorpe, Jonathan D. (author): Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB)

Hermann, Andreas (author): Translational Neurodegeneration Section, Albrecht-Kossel, Department of Neurology, University Medical Center Rostock, University of Rostock, Rostock, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Rostock/Greifswald, Rostock, Germany; Center for Transdisciplinary Neurosciences Rostock (CTNR), University Medical Center Rostock, University of Rostock, Rostock, Germany

show less...

(creator_code:org_t)

2022-04-06
2022
English.
In: Cells. - : MDPI. - 2073-4409. ; 11:7

Related links:: https://doi.org/10.3...; show more...; https://umu.diva-por... (primary) (Raw object); https://urn.kb.se/re...; https://doi.org/10.3...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Little is known about the early pathogenic events by which mutant superoxide dismutase 1 (SOD1) causes amyotrophic lateral sclerosis (ALS). This lack of mechanistic understanding is a major barrier to the development and evaluation of efficient therapies. Although protein aggregation is known to be involved, it is not understood how mutant SOD1 causes degeneration of motoneurons (MNs). Previous research has relied heavily on the overexpression of mutant SOD1, but the clinical relevance of SOD1 overexpression models remains questionable. We used a human induced pluripotent stem cell (iPSC) model of spinal MNs and three different endogenous ALS-associated SOD1 mutations (D90Ahom, R115Ghet or A4Vhet) to investigate early cellular disturbances in MNs. Although enhanced misfolding and aggregation of SOD1 was induced by proteasome inhibition, it was not affected by activation of the stress granule pathway. Interestingly, we identified loss of mitochondrial, but not lysosomal, integrity as the earliest common pathological phenotype, which preceded elevated levels of insoluble, aggregated SOD1. A super-elongated mitochondrial morphology with impaired inner mitochondrial membrane potential was a unifying feature in mutant SOD1 iPSC-derived MNs. Impaired mitochondrial integrity was most prominent in mutant D90Ahom MNs, whereas both soluble disordered and detergent-resistant misfolded SOD1 was more prominent in R115Ghet and A4Vhet mutant lines. Taking advantage of patient-specific models of SOD1-ALS in vitro, our data suggest that mitochondrial dysfunction is one of the first crucial steps in the pathogenic cascade that leads to SOD1-ALS and also highlights the need for individualized medical approaches for SOD1-ALS.

Find in a library

Cells (Search for host publication in LIBRIS)

To the university's database

1 of 2
Previous record
Next record
To hitlist

Find more in SwePub

By the author/editor: Günther, René; Pal, Arun; Williams, Chloe; Zimyanin, Vitaly ...; Liehr, Maria; von Neubeck, Clä ...; show more...; Krause, Mechthil ...; Parab, Mrudula G ...; Petri, Susanne; Kalmbach, Norman; Marklund, Stefan ...; Sterneckert, Jar ...; Andersen, Peter ...; Wegner, Florian; Gilthorpe, Jonat ...; Hermann, Andreas; show less...

About the subject

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

Articles in the publication: Cells

By the university: Umeå University

Search outside SwePub

Extend your search to:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se

Alteration of Mitochondrial Integrity as Upstream Event in the Pathophysiology of SOD1-ALS

Subject headings

Keyword

Publication and Content Type

Find in a library

To the university's database

Find more in SwePub

Search outside SwePub