Change search
ReferencesLink to record
Permanent link

Direct link
Low autophagy capacity implicated in motor system vulnerability to mutant superoxide dismutase
Umeå University, Faculty of Medicine, Department of Medical Biosciences.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Medical Biosciences.
2016 (English)In: Acta neuropathologica communications, ISSN 1509-409X, E-ISSN 2051-5960, Vol. 4, 6Article in journal (Refereed) PublishedText
Abstract [en]

Introduction: The motor system is selectively vulnerable to mutations in the ubiquitously expressed aggregation-prone enzyme superoxide dismutase-1 (SOD1).

Results: Autophagy clears aggregates, and factors involved in the process were analyzed in multiple areas of the CNS from human control subjects (n = 10) and amyotrophic lateral sclerosis (ALS) patients (n = 18) with or without SOD1 mutations. In control subjects, the key regulatory protein Beclin 1 and downstream factors were remarkably scarce in spinal motor areas. In ALS patients, there was evidence of moderate autophagy activation and also dysregulation. These changes were largest in SOD1 mutation carriers. To explore consequences of low autophagy capacity, effects of a heterozygous deletion of Beclin 1 were examined in ALS mouse models expressing mutant SOD1s. This caused earlier SOD1 aggregation, onset of symptoms, motor neuron loss, and a markedly shortened survival. In contrast, the levels of soluble misfolded SOD1 species were reduced.

Conclusions: The findings suggest that an inherent low autophagy capacity might cause the vulnerability of the motor system, and that SOD1 aggregation plays a crucial role in the pathogenesis.

Place, publisher, year, edition, pages
2016. Vol. 4, 6
Keyword [en]
Amyotrophic lateral sclerosis, Autophagy, Motor system vulnerability, Protein aggregates, Superoxide sumutase-1
National Category
URN: urn:nbn:se:umu:diva-116740DOI: 10.1186/s40478-016-0274-yISI: 000368653000001PubMedID: 26810478OAI: diva2:904823
Available from: 2016-02-19 Created: 2016-02-11 Last updated: 2016-02-24Bibliographically approved

Open Access in DiVA

fulltext(2869 kB)30 downloads
File information
File name FULLTEXT01.pdfFile size 2869 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Tokuda, EiichiBrännström, ThomasAndersen, Peter M.Marklund, Stefan L.
By organisation
Department of Medical BiosciencesDepartment of Pharmacology and Clinical Neuroscience
In the same journal
Acta neuropathologica communications

Search outside of DiVA

GoogleGoogle Scholar
Total: 30 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 65 hits
ReferencesLink to record
Permanent link

Direct link