EMANUELA D'ACUNTO

Dottoressa di ricerca

ciclo: XXXII



Titolo della tesi: Serpin function and disease: cellular toxicity of neuroserpin polymers and novel roles of alpha1-antitrypsin

The serpinopathies are due to misfolding and intracellular polymerisation of mutant serpin variants within the endoplasmic reticulum of the cell of synthesis and can be classified as conformational diseases, which arise when proteins undergo self-association and tissue deposition (Carrell and Lomas, 1997). Examples of human mutant serpins accumulating and causing a toxic gain of function are alpha1 antitrypsin variants underlying liver cirrhosis and mutants of neuroserpin causing the dementia familial encephalopathy with neuroserpin inclusion bodies (FENIB) (Roussel et al., 2011). Here we investigate with diverse approaches very different aspects of both pathologies. In the case of FENIB, following previous work in our laboratory in which we demonstrated the presence of oxidative stress in a novel neuronal model for FENIB neurodegeneration (Guadagno et al., 2017), we concentrate on cellular aspects of neuroserpin polymer toxicity, describing alterations in the morphology and function of the mitochondrial network and their interconnection with oxidative stress and changes in the communication between ER and mitochondria. Regarding alpha1 antitrypsin deficiency, we present the development and characterisation of functional monoclonal antibodies to explore the immunomodulatory roles of this protein.

Produzione scientifica

11573/1709621 - 2024 - Probing of the reactive center loop region of alpha-1-antitrypsin by mutagenesis predicts new type-2 dysfunctional variants
Denardo, Andrea; Ben Khlifa, Emna; Bignotti, Mattia; Giuliani, Roberta; D’Acunto, Emanuela; Miranda, Elena; Irving, James A.; Fra, Annamaria - 01a Articolo in rivista
rivista: CELLULAR AND MOLECULAR LIFE SCIENCES (Birkhaeuser Verlag AG:Viaduktstrasse 42-44, CH 4051 Basel Switzerland:011 41 61 2050707, EMAIL: subscriptions@birkhauser.ch, INTERNET: http://www.birkhauser.ch, Fax: 011 41 61 2050792) pp. - - issn: 1420-682X - wos: WOS:001124770800002 (1) - scopus: 2-s2.0-85179640100 (1)

11573/1651297 - 2022 - Polymerogenic neuroserpin causes mitochondrial alterations and activates NFκB but not the UPR in a neuronal model of neurodegeneration FENIB
D'acunto, E; Gianfrancesco, L; Serangeli, I; D'orsi, M; Sabato, V; Guadagno, N A; Bhosale, G; Caristi, S; Failla, A V; De Jaco, A; Cacci, E; Duchen, M R; Lupo, G; Galliciotti, G; Miranda, E - 01a Articolo in rivista
rivista: CELLULAR AND MOLECULAR LIFE SCIENCES (Birkhaeuser Verlag AG:Viaduktstrasse 42-44, CH 4051 Basel Switzerland:011 41 61 2050707, EMAIL: subscriptions@birkhauser.ch, INTERNET: http://www.birkhauser.ch, Fax: 011 41 61 2050792) pp. - - issn: 1420-682X - wos: WOS:000828696400008 (2) - scopus: 2-s2.0-85134581511 (4)

11573/1566754 - 2021 - Neuroserpin: structure, function, physiology and pathology
D'acunto, E.; Fra, A.; Visentin, C.; Manno, M.; Ricagno, S.; Galliciotti, G.; Miranda, E. - 01g Articolo di rassegna (Review)
rivista: CELLULAR AND MOLECULAR LIFE SCIENCES (Birkhaeuser Verlag AG:Viaduktstrasse 42-44, CH 4051 Basel Switzerland:011 41 61 2050707, EMAIL: subscriptions@birkhauser.ch, INTERNET: http://www.birkhauser.ch, Fax: 011 41 61 2050792) pp. 6409-6430 - issn: 1420-682X - wos: WOS:000685601300001 (24) - scopus: 2-s2.0-85112757258 (25)

11573/1552616 - 2021 - G392E neuroserpin causing the dementia FENIB is secreted from cells but is not synaptotoxic
Ingwersen, T.; Linnenberg, C.; D'acunto, E.; Temori, S.; Paolucci, I.; Wasilewski, D.; Mohammadi, B.; Kirchmair, J.; Glen, R. C.; Miranda, E.; Glatzel, M.; Galliciotti, G. - 01a Articolo in rivista
rivista: SCIENTIFIC REPORTS (London: Springer Nature London: Nature Publishing Group) pp. 1-13 - issn: 2045-2322 - wos: WOS:000642742500097 (7) - scopus: 2-s2.0-85104605840 (7)

11573/1552606 - 2021 - The Importance of N186 in the Alpha-1-Antitrypsin Shutter Region Is Revealed by the Novel Bologna Deficiency Variant
Ronzoni, Riccardo; Ferrarotti, Ilaria; D'acunto, Emanuela; Balderacchi, Alice M; Ottaviani, Stefania; Lomas, David A; Irving, James A; Miranda, Elena; Fra, Annamaria - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel: MDPI Center) pp. -1 - issn: 1422-0067 - wos: WOS:000660230700001 (5) - scopus: 2-s2.0-85106430982 (7)

11573/1172708 - 2018 - Cellular models for the serpinopathies
Fra, Annamaria; D'acunto, Emanuela; Laffranchi, Mattia; Miranda Banos, Maria Elena - 02a Capitolo o Articolo
libro: Methods in Molecular Biology - (978-1-4939-8644-6; 978-1-4939-8645-3)

11573/1175716 - 2018 - Circulating miR-127-3p as a Potential Biomarker for Differential Diagnosis in Frontotemporal Dementia
Piscopo, P; Grasso, M; Puopolo, M; D'acunto, E; Talarico, G; Crestini, A; Gasparini, M; Campopiano, R; Gambardella, S; Castellano, Ae; Bruno, G; Denti, Ma; Confaloni, A - 01g Articolo di rassegna (Review)
rivista: JOURNAL OF ALZHEIMER'S DISEASE (Netherlands: IOS Press) pp. 455-464 - issn: 1387-2877 - wos: WOS:000442247800010 (20) - scopus: 2-s2.0-85058614449 (23)

11573/950793 - 2017 - Neuroserpin polymers cause oxidative stress in a neuronal model of the dementia FENIB
Guadagno, Noemi Antonella; Moriconi, Claudia; Licursi, Valerio; D'acunto, Emanuela; Nisi, Paola Serena; Carucci, Nicoletta; De Jaco, Antonella; Cacci, Emanuele; Negri, Rodolfo; Lupo, Giuseppe; Miranda Banos, Maria Elena - 01a Articolo in rivista
rivista: NEUROBIOLOGY OF DISEASE (Academic Press Incorporated:6277 Sea Harbor Drive:Orlando, FL 32887:(800)543-9534, (407)345-4100, EMAIL: ap@acad.com, INTERNET: http://www.idealibrary.com, Fax: (407)352-3445) pp. 32-44 - issn: 0969-9961 - wos: WOS:000401683200004 (22) - scopus: 2-s2.0-85016948857 (23)

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