BRICHOS Domains Efficiently Delay Fibrillation of Amyloid β-Peptide

Willander, Hanna; Presto, Jenny; Askarieh, Glareh; Biverstål, Henrik; Frohm, Birgitta; Knight, Stefan D.; Johansson, Jan; Linse, Sara

doi:10.1074/jbc.m112.393157

Cited by 132 publications

(173 citation statements)

References 66 publications

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“…With respect to Aβ(1-40), GKN1 exibits its anti-Aβ aggregation activity at substoichiometric concentrations (1:10 rGKN1/Aβ molar ratio), in accord with data reported for the recombinant proSP-C and BRI2 BRICHOS domains 28,29 . Regarding the activity of GKN1 toward Aβ(1-42), no data is yet available however, it might be possible that GKN1 behaves similarly to Bri2 and pro-SP-C BRICHOS domains 29 . It must be pointed out that Aβ(1-42) represents the most AD-relevant amyloid peptide 30 .…”

Section: Gkn1 and The Anti-amyloidogenic Property Of Brichos Domainsupporting

confidence: 70%

Human Gastrokine 1 and its anti-amyloidogenic properties

Stadio¹,

Altieri²,

Minopoli³

et al. 2017

J Neurol Neuromedicine

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Gastrokine 1 (GKN1) is a 18 kDa stomach protein highly expressed in normal gastric tissue but absent in gastric cancer. GKN1 plays its major role in maintaining gastric mucosal integrity. Because of the presence in its central region of a BRICHOS domain, GKN1 is characterized by multifunctional properties since it interacts and regulates the activity of several proteins. The BRICHOS domain consists of about 100 amino acids and has been found in protein families often associated with major human diseases like familial British and Danish dementia (BRI2) or respiratory distress syndrome (surfactant protein C) (SP-C), both associated with amyloid formation. It has been shown that BRICHOS is a chaperon domain that has the property of binding precursor protein regions with high β-sheet tendencies, thereby preventing them from amyloid formation. Like the BRICHOS domains from BRI2 and SP-C precursor (proSP-C), also GKN1 is able to prevent fibrils formation of amyloidbeta peptide (Aβ) and to interact with the C-terminal region of APP thus hindering the γ-secretase proteolytic sites. Indeed, amyloid is of great medical importance since it originates in several major fatal diseases such as Alzheimer, Parkinson and diabetes mellitus. The results collected until now on the BRICHOS properties of GKN1 and those from other BRICHOS suggest that the different amyloids recognized by BRICHOS should contain similar structural elements therefore, the BRICHOS domain represents a potential powerfull tool for therapeutic approaches against amyloid associated diseases.

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Section: Gkn1 and The Anti-amyloidogenic Property Of Brichos Domainsupporting

confidence: 70%

Human Gastrokine 1 and its anti-amyloidogenic properties

Stadio¹,

Altieri²,

Minopoli³

et al. 2017

J Neurol Neuromedicine

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“…Sub-stoichiometric amounts of recombinant BRICHOS domains of human proSP-C and Bri2 prevent fibril formation of both A␤ 40 and A␤ 42 in vitro (37). Recently, it was shown that proSP-C BRICHOS specifically inhibits the secondary nucleation of A␤ 42 aggregation (47).…”

Section: Mode Of Action Of the Brichos Domainmentioning

confidence: 99%

“…The proSP-C BRICHOS domain hence may be a chaperone tailored to interact with a particularly amyloidogenic sequence (34,35). Other BRICHOS homologues possess similar chaperone activity (36,37). Most importantly, the BRICHOS-containing Bri2 protein (also known as ITM2B), which is expressed in the central nervous system, is closely linked to protein aggregation diseases.…”

Section: Brichos: a Multi-purpose Anti-amyloid Chaperonementioning

confidence: 99%

“…ProSP-C BRICHOS lacks strict sequence specificity (44) and is also able to inhibit amyloid formation of other peptides and proteins, including A␤ (37). Expression of A␤ 42 in the brain of transgenic Drosophila flies decreases longevity and impairs locomotor activity, correlated with A␤ aggregation and deposition in the brain (45).…”

Section: Brichos: a Multi-purpose Anti-amyloid Chaperonementioning

confidence: 99%

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Specific Chaperones and Regulatory Domains in Control of Amyloid Formation

Landreh

Rising

Presto

et al. 2015

Journal of Biological Chemistry

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Many proteins can form amyloid-like fibrils in vitro, but only about 30 amyloids are linked to disease, whereas some proteins form physiological amyloid-like assemblies. This raises questions of how the formation of toxic protein species during amyloidogenesis is prevented or contained in vivo. Intrinsic chaperoning or regulatory factors can control the aggregation in different protein systems, thereby preventing unwanted aggregation and enabling the biological use of amyloidogenic proteins. The molecular actions of these chaperones and regulators provide clues to the prevention of amyloid disease, as well as to the harnessing of amyloidogenic proteins in medicine and biotechnology.

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“…In our experiment, the lag time was calculated by fitting established equations to the curve. 34 The ThT fluorescence data, which represented the kinetics in the presence and absence of seeds, showed that gel fibrils did not affect the aggregation of WT α-Syn protein. In contrast, preformed fibril seeds from full-length protein aggregated WT α-Syn protein much faster, as evidenced by the undetectable lag time (Figure 3b).…”

Section: Toxicity and Seeding Capacity Of Amyloid Hydrogelsmentioning

confidence: 99%

Implantable amyloid hydrogels for promoting stem cell differentiation to neurons

et al. 2016

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We report a new class of amyloid-inspired peptide hydrogels that was designed and based on α-synuclein protein for which hydrogel formation is triggered by various stimuli, such as heating/cooling or changes in pH. The peptides resemble a cross-β-sheet-rich amyloid, and they assemble into a nanofibrous meshwork that mimics the natural extracellular matrix. Our design principle allows easy manipulation of the gelator sequence to exploit the desirable properties of amyloids for use in cell replacement therapies for neurodegenerative diseases. The amyloid hydrogels facilitate the attachment and neuronal differentiation of mesenchymal stem cells (MSCs) and assist in the delivery and engraftment of MSCs in the substantia nigra and caudate putamen of a Parkinsonian mouse model.

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BRICHOS Domains Efficiently Delay Fibrillation of Amyloid β-Peptide

Cited by 132 publications

References 66 publications

Human Gastrokine 1 and its anti-amyloidogenic properties

Human Gastrokine 1 and its anti-amyloidogenic properties

Specific Chaperones and Regulatory Domains in Control of Amyloid Formation

Implantable amyloid hydrogels for promoting stem cell differentiation to neurons

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