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

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
Depositing User:	Lovorka Čaja
Date Deposited:	11 Jul 2024 11:32
URI:	https://fulir.irb.hr:/id/eprint/8932
DOI:	10.3390/biomedicines11061599

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