Emerging Trends in the Field of Inflammation and Proteinopathy in ALS/FTD Spectrum Disorder

De Marchi, Fabiola; Franjkic, Toni; Schito, Paride; Russo, Tommaso; Nimac, Jerneja; Chami, Anna A.; Mele, Angelica; Vidatic, Lea; Kriz, Jasna; Julien, Jean-Pierre; Apic, Gordana; Russell, Robert B.; Rogelj, Boris; Cannon, Jason R.; Baralle, Marco; Agosta, Federica; Hećimović, Silva; Mazzini, Letizia; Buratti, Emanuele; Munitic, Ivana (2023) Emerging Trends in the Field of Inflammation and Proteinopathy in ALS/FTD Spectrum Disorder. Biomedicines, 11 (6). ISSN 2227-9059

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Abstract

first_page settings Order Article Reprints Open AccessReview Emerging Trends in the Field of Inflammation and Proteinopathy in ALS/FTD Spectrum Disorder by Fabiola De Marchi 1 [ORCID] , Toni Franjkic 2,3, Paride Schito 4 [ORCID] , Tommaso Russo 4, Jerneja Nimac 5,6, Anna A. Chami 7 [ORCID] , Angelica Mele 1, Lea Vidatic 8, Jasna Kriz 7 [ORCID] , Jean-Pierre Julien 7, Gordana Apic 3, Robert B. Russell 9 [ORCID] , Boris Rogelj 5,10, Jason R. Cannon 11,12, Marco Baralle 13, Federica Agosta 14, Silva Hecimovic 8 [ORCID] , Letizia Mazzini 1,*, Emanuele Buratti 15,* [ORCID] and Ivana Munitic 2,* [ORCID] 1 Department of Neurology and ALS Centre, University of Piemonte Orientale, Maggiore Della Carità Hospital, Corso Mazzini 18, 28100 Novara, Italy 2 Laboratory for Molecular Immunology, Department of Biotechnology, University of Rijeka, R. Matejcic 2, 51000 Rijeka, Croatia 3 Metisox, Cambridge CB24 9NL, UK 4 Department of Neurology & Neuropathology Unit, Institute of Experimental Neurology (INSPE), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy 5 Department of Biotechnology, Jozef Stefan Institute, SI-1000 Ljubljana, Slovenia 6 Graduate School of Biomedicine, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia 7 CERVO Research Centre, Laval University, Quebec City, QC G1J 2G3, Canada 8 Laboratory for Neurodegenerative Disease Research, Division of Molecular Medicine, Ruder Boskovic Institute, 10000 Zagreb, Croatia 9 Cell Networks, University of Heidelberg, 69117 Heidelberg, Germany 10 Faculty of Chemistry and Chemical Technology, University of Ljubljana, SI-1000 Ljubljana, Slovenia add Show full affiliation list * Authors to whom correspondence should be addressed. Biomedicines 2023, 11(6), 1599; https://doi.org/10.3390/biomedicines11061599 Submission received: 28 April 2023 / Revised: 27 May 2023 / Accepted: 29 May 2023 / Published: 31 May 2023 (This article belongs to the Special Issue Editorial Board Members’ Collection Series: “Amyotrophic Lateral Sclerosis: The Present and the Future of the Research”) Download keyboard_arrow_down Browse Figures Review Reports Versions Notes Abstract Proteinopathy and neuroinflammation are two main hallmarks of neurodegenerative diseases. They also represent rare common events in an exceptionally broad landscape of genetic, environmental, neuropathologic, and clinical heterogeneity present in patients. Here, we aim to recount the emerging trends in amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) spectrum disorder. Our review will predominantly focus on neuroinflammation and systemic immune imbalance in ALS and FTD, which have recently been highlighted as novel therapeutic targets. A common mechanism of most ALS and ~50% of FTD patients is dysregulation of TAR DNA-binding protein 43 (TDP-43), an RNA/DNA-binding protein, which becomes depleted from the nucleus and forms cytoplasmic aggregates in neurons and glia. This, in turn, via both gain and loss of function events, alters a variety of TDP-43-mediated cellular events. Experimental attempts to target TDP-43 aggregates or manipulate crosstalk in the context of inflammation will be discussed. Targeting inflammation, and the immune system in general, is of particular interest because of the high plasticity of immune cells compared to neurons.

Item Type:

Article

Uncontrolled Keywords:

amyotrophic lateral sclerosis; frontotemporal degeneration; inflammation; proteinopathy; neurodegenerative diseases

Subjects:

BIOMEDICINE AND HEALTHCARE

Divisions:

Division of Molecular Medicine

Projects:

Project title	Project leader	Project code	Project type
Kontrola neurodegeneracije moduliranjem sprege između upale i proteinopatije-ImmunoModifyCNS	Ivana Munitić	IP-2018-01-8563	HRZZ
Generacija i molekularna karakterizacija in vitro i in vivo modela amiotrofične lateralne skleroze-	Ivana Munitić	Uniri-biomed-18-211	NadSve
Molekularni mehanizam neurodegeneracije u Niemann-Pickovoj bolesti tip C-neuroNiPiC	Silva Katušić Hećimović	IP-2016-06-2799	HRZZ