Evidence map›Paper›PMID 32414108›Full record

ArticleInternational journal of molecular sciences2020

Enhanced Clearance of Neurotoxic Misfolded Proteins by the Natural Compound Berberine and Its Derivatives.

Paola Rusmini, Riccardo Cristofani, Barbara Tedesco, Veronica Ferrari, Elio Messi, Margherita Piccolella, Elena Casarotto, Marta Chierichetti, Maria Elena Cicardi, Mariarita Galbiati and 4 more

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Article
  2. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Paola RusminiDipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Dipartimento di Eccellenza 2018-2022, Centro di Eccellenza sulle Malattie Neurodegenerative, Università degli Studi di Milano, 20133 Milan, Italy.
Riccardo CristofaniDipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Dipartimento di Eccellenza 2018-2022, Centro di Eccellenza sulle Malattie Neurodegenerative, Università degli Studi di Milano, 20133 Milan, Italy.
Barbara TedescoDipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Dipartimento di Eccellenza 2018-2022, Centro di Eccellenza sulle Malattie Neurodegenerative, Università degli Studi di Milano, 20133 Milan, Italy.
Veronica FerrariDipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Dipartimento di Eccellenza 2018-2022, Centro di Eccellenza sulle Malattie Neurodegenerative, Università degli Studi di Milano, 20133 Milan, Italy.
Elio MessiDipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Dipartimento di Eccellenza 2018-2022, Centro di Eccellenza sulle Malattie Neurodegenerative, Università degli Studi di Milano, 20133 Milan, Italy.
Margherita PiccolellaDipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Dipartimento di Eccellenza 2018-2022, Centro di Eccellenza sulle Malattie Neurodegenerative, Università degli Studi di Milano, 20133 Milan, Italy.
Elena CasarottoDipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Dipartimento di Eccellenza 2018-2022, Centro di Eccellenza sulle Malattie Neurodegenerative, Università degli Studi di Milano, 20133 Milan, Italy.
Marta ChierichettiDipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Dipartimento di Eccellenza 2018-2022, Centro di Eccellenza sulle Malattie Neurodegenerative, Università degli Studi di Milano, 20133 Milan, Italy.
Maria Elena CicardiDipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Dipartimento di Eccellenza 2018-2022, Centro di Eccellenza sulle Malattie Neurodegenerative, Università degli Studi di Milano, 20133 Milan, Italy.
Mariarita GalbiatiDipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Dipartimento di Eccellenza 2018-2022, Centro di Eccellenza sulle Malattie Neurodegenerative, Università degli Studi di Milano, 20133 Milan, Italy.
Cristina GeroniNaxospharma srl, 20026 Novate Milanese, Milan, Italy.
Paolo LombardiNaxospharma srl, 20026 Novate Milanese, Milan, Italy.
Valeria CrippaDipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Dipartimento di Eccellenza 2018-2022, Centro di Eccellenza sulle Malattie Neurodegenerative, Università degli Studi di Milano, 20133 Milan, Italy.
Angelo PolettiDipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Dipartimento di Eccellenza 2018-2022, Centro di Eccellenza sulle Malattie Neurodegenerative, Università degli Studi di Milano, 20133 Milan, Italy.

Funding

AFM-Téléthon 16406Agenzia Italiana del Farmaco, Ministero della Salute Co_ALSEU Joint Programme - Neurodegenerative Disease Research 01ED1601A, CureALSFondazione Cariplo 2014-0686Fondazione Cariplo 2017_0747Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica ALS_GranulopathyFondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica ALS_HSPB8Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica MLOpathyFondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica Target-RANFondazione Regionale per la Ricerca Biomedica (FRRB) (Regione Lombardia TRANS_ALS, project nr. 2015-0023Fondazione Telethon GGP14039Fondazione Telethon GGP19128Kennedy's disease association 2018 GrantMinistero della Salute GR-2011-02347198Ministero dell'Istruzione, dell'Università e della Ricerca 2017F2A2C5Ministero dell'Istruzione, dell'Università e della Ricerca Fondo per il Finanziamento delle Attività Base di Ricerca (FFABR)Ministero dell'Istruzione, dell'Università e della Ricerca PRIN 2015LFPNMNUniversità degli Studi di Milano Bando Straordinario per Progetti Interdipartimentali (Bando SEED 2019: #TDP-43-iPSCUniversità degli Studi di Milano Piano di sviluppo UNIMI - linea B
6 · The paper itself

Abstract

backgroundAccumulation of misfolded proteins is a common hallmark of several neurodegenerative disorders (NDs) which results from a failure or an impairment of the protein quality control (PQC) system. The PQC system is composed by chaperones and the degradative systems (proteasome and autophagy). Mutant proteins that misfold are potentially neurotoxic, thus strategies aimed at preventing their aggregation or at enhancing their clearance are emerging as interesting therapeutic targets for NDs.

methodsWe tested the natural alkaloid berberine (BBR) and some derivatives for their capability to enhance misfolded protein clearance in cell models of NDs, evaluating which degradative pathway mediates their action.

resultsWe found that both BBR and its semisynthetic derivatives promote degradation of mutant androgen receptor (ARpolyQ) causative of spinal and bulbar muscular atrophy, acting mainly via proteasome and preventing ARpolyQ aggregation. Overlapping effects were observed on other misfolded proteins causative of amyotrophic lateral sclerosis, frontotemporal-lobar degeneration or Huntington disease, but with selective and specific action against each different mutant protein.

conclusionsBBR and its analogues induce the clearance of misfolded proteins responsible for NDs, representing potential therapeutic tools to counteract these fatal disorders.

Indexed as

Amyotrophic Lateral SclerosisAutophagyBerberineBiological ProductsCell LineFrontotemporal DementiaHumansMolecular ChaperonesMutant ProteinsNeurotoxicity SyndromesProteasome Endopeptidase ComplexProtein Aggregation, PathologicalProteostasis DeficienciesBerberineBiological ProductsMolecular ChaperonesMutant ProteinsProteasome Endopeptidase Complexamyotrophic lateral sclerosisautophagyberberinefrontotemporal dementiamisfoldingneurodegenerationproteasomeprotein aggregationspinal and bulbar muscular atrophy

Identifiers

PMID32414108
PMCPMC7279252

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.