The chaperone domain BRICHOS prevents CNS toxicity of amyloid-beta peptide in Drosophila melanogaster

Schultz, Sebastian (author)

Crowther, Damian (author)

Linse, Sara (author): Lund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH

Winblad, Bengt (author)

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

Johansson, Jan (author): Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB),Karolinska Institute,Tallinn University

(creator_code:org_t)

2014-01-01
2014
English.
In: Disease Models and Mechanisms. - : The Company of Biologists. - 1754-8411 .- 1754-8403. ; 7:6, s. 659-665

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Abstract Subject headings

Aggregation of the amyloid-beta peptide (A beta) into toxic oligomers and amyloid fibrils is linked to the development of Alzheimer's disease (AD). Mutations of the BRICHOS chaperone domain are associated with amyloid disease and recent in vitro data show that BRICHOS efficiently delays A beta 42 oligomerization and fibril formation. We have generated transgenic Drosophila melanogaster flies that express the A beta 42 peptide and the BRICHOS domain in the central nervous system (CNS). Co-expression of A beta 42 and BRICHOS resulted in delayed A beta 42 aggregation and dramatic improvements of both lifespan and locomotor function compared with flies expressing A beta 42 alone. Moreover, BRICHOS increased the ratio of soluble: insoluble A beta 42 and bound to deposits of A beta 42 in the fly brain. Our results show that the BRICHOS domain efficiently reduces the neurotoxic effects of A beta 42, although significant A beta 42 aggregation is taking place. We propose that BRICHOS-based approaches should be explored with an aim towards the future prevention and treatment of AD.

NATURVETENSKAP -- Biologi (hsv//swe)
NATURAL SCIENCES -- Biological Sciences (hsv//eng)
NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)

By the author/editor: Hermansson, Erik; Schultz, Sebasti ...; Crowther, Damian; Linse, Sara; Winblad, Bengt; Westermark, Guni ...; show more...; Johansson, Jan; Presto, Jenny; show less...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Cell Biology

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Medical Biotechn ...; and Medical Biotechn ...

By the university: Lund University; Swedish University of Agricultural Sciences; Uppsala University

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