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

• 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.

Ämnesord

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)

Nyckelord

Amyloid

Alzheimer's disease

Protein misfolding

Chaperone

Amyloid

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art (ämneskategori)

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