This page in English
Laddar profil information

Om mig

Jag disputerade vid Uppsala Universitet 2006 och min avhandling handlade om biosyntes av heparansulfat.

2011 började jag som postdoktor vid KI och 2012 fick jag en anställning som forskarassistent.

Forskningsbeskrivning

I min forskningsgrupp studerar vi en proteindomän som kallas BRICHOS, som har hittats i över 300 olika proteiner. 

BRICHOS har en anti-amyloid chaperon aktivitet och vi har visat att BRICHOS effektivt kan förhindra amyloidbildning, in vitro, av amyloid-beta peptiden (Abeta), som bildar plack i hjärnan hos Alzheimerpatienter. När Abeta börjar aggregera och bilda amyloida plack uppstår toxiska intermediärer, som man tror är en orsak till neurodegeneration hos AD patienter.

Vi studerar hur BRICHOS interagerar med Abeta och förhindar dess amyloidbildning och toxicitet. Vi använder oss av biokemiska och cellbiologiska metoder, men har även tidigare använt en in vivo modell i Drosophila melanogaster (bananfluga). Abeta ger upphov till toxicitet i en bananflugas hjärna och vi studerar om olika BRICHOS domäner kan förhindra denna toxicitet från Abeta in vivo i en flughjärna.

Våra resultat är väldigt lovande och vårt mål är att undersöka om BRICHOS kan vara en möjlig behandlingsstrategi vid Alzheimers sjukdom.

Publikationer

BRICHOS binds to a designed amyloid-forming β-protein and reduces proteasomal inhibition and aggresome formation
Dolfe L, Winblad B, Johansson J, Presto J
The Biochemical journal 2016;473(2):167-78

Current and future treatment of amyloid diseases
Ankarcrona M, Winblad B, Monteiro C, Fearns C, Powers Et, Johansson J, et al
Journal of internal medicine 2016;280(2):177-202

Kinetic analysis reveals the diversity of microscopic mechanisms through which molecular chaperones suppress amyloid formation
Arosio P, Michaels Tc, Linse S, Månsson C, Emanuelsson C, Presto J, et al
Nature communications 2016;7():10948-

A molecular chaperone breaks the catalytic cycle that generates toxic Aβ oligomers
Cohen Si, Arosio P, Presto J, Kurudenkandy Fr, Biverstål H, Dolfe L, et al
Nature structural & molecular biology 2015;22(3):207-13

BRI2 ectodomain affects Aβ42 fibrillation and tau truncation in human neuroblastoma cells
Del Campo M, Oliveira Cr, Scheper W, Zwart R, Korth C, Müller-schiffmann A, et al
Cellular and molecular life sciences : CMLS 2015;72(8):1599-611

Dissociation of a BRICHOS trimer into monomers leads to increased inhibitory effect on Aβ42 fibril formation
Biverstål H, Dolfe L, Hermansson E, Leppert A, Reifenrath M, Winblad B, et al
Biochimica et biophysica acta 2015;1854(8):835-43

Folding and Intramembraneous BRICHOS Binding of the Prosurfactant Protein C Transmembrane Segment
Sáenz A, Presto J, Lara P, Akinyi-oloo L, García-fojeda B, Nilsson I, et al
The Journal of biological chemistry 2015;290(28):17628-41

Specific chaperones and regulatory domains in control of amyloid formation
Landreh M, Rising A, Presto J, Jörnvall H, Johansson J
The Journal of biological chemistry 2015;290(44):26430-6

Amyloid-β-induced action potential desynchronization and degradation of hippocampal gamma oscillations is prevented by interference with peptide conformation change and aggregation
Kurudenkandy Fr, Zilberter M, Biverstål H, Presto J, Honcharenko D, Strömberg R, et al
The Journal of neuroscience : the official journal of the Society for Neuroscience 2014;34(34):11416-25

Live-cell topology assessment of URG7, MRP6₁₀₂ and SP-C using glycosylatable green fluorescent protein in mammalian cells
Lee H, Lara P, Ostuni A, Presto J, Johansson J, Nilsson I, et al
Biochemical and biophysical research communications 2014;450(4):1587-92

The chaperone domain BRICHOS prevents CNS toxicity of amyloid-β peptide in Drosophila melanogaster
Hermansson E, Schultz S, Crowther D, Linse S, Winblad B, Westermark G, et al
Disease models & mechanisms 2014;7(6):659-65

The BRICHOS domain, amyloid fibril formation, and their relationship
Knight Sd, Presto J, Linse S, Johansson J
Biochemistry 2013;52(43):7523-31

BRICHOS domains efficiently delay fibrillation of amyloid β-peptide
Willander H, Presto J, Askarieh G, Biverstål H, Frohm B, Knight Sd, et al
The Journal of biological chemistry 2012;287(37):31608-17

Control of amyloid assembly by autoregulation
Landreh M, Johansson J, Rising A, Presto J, Jörnvall H
The Biochemical journal 2012;447(2):185-92

High-resolution structure of a BRICHOS domain and its implications for anti-amyloid chaperone activity on lung surfactant protein C
Willander H, Askarieh G, Landreh M, Westermark P, Nordling K, Keranen H, et al
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2012;109(7):2325-9

BRICHOS domain associated with lung fibrosis, dementia and cancer - a chaperone that prevents amyloid fibril formation?
Willander H, Hermansson E, Johansson J, Presto J
FEBS JOURNAL 2011;278(20):3893-904

Heparan sulfate/heparin promotes transthyretin fibrillization through selective binding to a basic motif in the protein
Noborn F, O'callaghan P, Hermansson E, Zhang Xa, Ancsin Jb, Damas Am, et al
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2011;108(14):5584-9

Conformational preferences of non-polar amino acid residues: an additional factor in amyloid formation
Johansson J, Nerelius C, Willander H, Presto J
Biochemical and biophysical research communications 2010;402(3):515-8

The Brichos domain of prosurfactant protein C can hold and fold a transmembrane segment
Johansson H, Eriksson M, Nordling K, Presto J, Johansson J
Protein science : a publication of the Protein Society 2009;18(6):1175-82

Heparan sulfate biosynthesis enzymes EXT1 and EXT2 affect NDST1 expression and heparan sulfate sulfation
Presto J, Thuveson M, Carlsson P, Busse M, Wilén M, Eriksson I, et al
Proceedings of the National Academy of Sciences of the United States of America 2008;105(12):4751-6

Heparin/heparan sulfate biosynthesis: processive formation of N-sulfated domains
Carlsson P, Presto J, Spillmann D, Lindahl U, Kjellén L
The Journal of biological chemistry 2008;283(29):20008-14

Contribution of EXT1, EXT2, and EXTL3 to heparan sulfate chain elongation
Busse M, Feta A, Presto J, Wilén M, Grønning M, Kjellén L, et al
The Journal of biological chemistry 2007;282(45):32802-10

Distinct effects on heparan sulfate structure by different active site mutations in NDST-1
Bengtsson J, Eriksson I, Kjellén L
Biochemistry 2003;42(7):2110-5

Visa alla publikationer