Abstract
Background: Therapeutic approaches targeting amyloid β42 (Aβ42) oligomers may represent a promising neuroprotective strategy for the prevention and treatment of Alzheimer's disease (AD).
Objective: In this study we evaluated the ability of bromelain, a plant cysteine protease derived from pineapple stems, to interact with synthetic Aβ42 monomers and oligomers. We also examined the ability of bromelain to interfere in vitro with synthetic Aβ42 aggregates in the cerebrospinal fluid (CSF) of Alzheimer's disease as well as of control patients affected by other neurological diseases.
Method: Both synthetic monomers and aggregates of Aβ42 were incubated in CSF with varying concentrations of bromelain. The effects of digestion were evaluated by Western Blot analysis using the specific monoclonal antibody 4G8 to identify the patterns of residual content of Aβ42. We further used rat primary cortical culture neurons (CN) to examine the cytotoxic action of this natural compound.
Results: We found that bromelain successfully degraded Aβ42 monomers and low and high molecular weight oligomers. Indeed, when bromelain preparations of 3 and 6 mU were added to the CSF, the residual amount of Aβ42 monomers and oligomers were significantly reduced when compared to the same standard Aβ42 preparations incubated in CSF without bromelain. Moreover, bromelain incubations of 0.1, 0.5, and 1 mU/ml were not toxic to CN, as compared to vehicle treated cells.
Conclusion: Overall, these results represent an important insight into the action of bromelain on Aβ42 oligomers, suggesting its potential use in the therapy of AD.
Keywords: Amyloid β42, aggregation, bromelain, Alzheimer's disease, AD therapy, prevention.
Current Alzheimer Research
Title:Bromelain Degrades Aβ1-42 Monomers and Soluble Aggregates: An In Vitro Study in Cerebrospinal Fluid of Alzheimer’s Disease Patients
Volume: 15 Issue: 7
Author(s): Giulia M. Sancesario*, Marzia Nuccetelli, Andrea Cerri, Joshua Zegeer, Cinzia Severini, Maria T. Ciotti, Massimo Pieri, Alessandro Martorana, Carlo Caltagirone, Robert Nistico and Sergio Bernardini
Affiliation:
- Department of Clinical and Behavioural Neurology, Santa Lucia Foundation IRCCS, Rome,Italy
Keywords: Amyloid β42, aggregation, bromelain, Alzheimer's disease, AD therapy, prevention.
Abstract: Background: Therapeutic approaches targeting amyloid β42 (Aβ42) oligomers may represent a promising neuroprotective strategy for the prevention and treatment of Alzheimer's disease (AD).
Objective: In this study we evaluated the ability of bromelain, a plant cysteine protease derived from pineapple stems, to interact with synthetic Aβ42 monomers and oligomers. We also examined the ability of bromelain to interfere in vitro with synthetic Aβ42 aggregates in the cerebrospinal fluid (CSF) of Alzheimer's disease as well as of control patients affected by other neurological diseases.
Method: Both synthetic monomers and aggregates of Aβ42 were incubated in CSF with varying concentrations of bromelain. The effects of digestion were evaluated by Western Blot analysis using the specific monoclonal antibody 4G8 to identify the patterns of residual content of Aβ42. We further used rat primary cortical culture neurons (CN) to examine the cytotoxic action of this natural compound.
Results: We found that bromelain successfully degraded Aβ42 monomers and low and high molecular weight oligomers. Indeed, when bromelain preparations of 3 and 6 mU were added to the CSF, the residual amount of Aβ42 monomers and oligomers were significantly reduced when compared to the same standard Aβ42 preparations incubated in CSF without bromelain. Moreover, bromelain incubations of 0.1, 0.5, and 1 mU/ml were not toxic to CN, as compared to vehicle treated cells.
Conclusion: Overall, these results represent an important insight into the action of bromelain on Aβ42 oligomers, suggesting its potential use in the therapy of AD.
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Cite this article as:
Sancesario M. Giulia *, Nuccetelli Marzia , Cerri Andrea, Zegeer Joshua , Severini Cinzia , Ciotti T. Maria, Pieri Massimo, Martorana Alessandro , Caltagirone Carlo , Nistico Robert and Bernardini Sergio , Bromelain Degrades Aβ1-42 Monomers and Soluble Aggregates: An In Vitro Study in Cerebrospinal Fluid of Alzheimer’s Disease Patients, Current Alzheimer Research 2018; 15 (7) . https://dx.doi.org/10.2174/1567205015666180123124851
DOI https://dx.doi.org/10.2174/1567205015666180123124851 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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