Transforming growth factor beta (TGFB) is a pleiotropic cytokine, known to be dysregulated in many neurodegenerative disorders and particularly in amyotrophic lateral sclerosis (ALS). This motor neuronal disease is non-cell autonomous, as it affects not only motor neurons, but also their surrounding glial cells, and their target skeletal muscle fibers. Here, we analyze the multiple roles of TGFB in these cell types, and how TGFB signaling is altered in ALS tissues. Data reported support a crucial involvement of TGFB in the etiology and progression of ALS, leading us to hypothesize that an imbalance of TGFB signaling, diminished at the pre-symptomatic stage and then increased with time, could be linked to ALS progression. A reduced stimulation of the TGFB pathway at the beginning of disease blocks its neuroprotective effects and promotes glutamate excitotoxicity. At later disease stages, the persistent activation of the TGFB pathway promotes an excessive microglial activation and strengthens muscular dysfunction. The therapeutic potential of TGFB is discussed here, in order to foster new approaches to treat ALS.
Multiple Roles of Transforming Growth Factor Beta in Amyotrophic Lateral Sclerosis / M. Galbiati, V. Crippa, P. Rusmini, R.M. Cristofani, E. Messi, M. Piccolella, B. Tedesco, V. Ferrari, E. Casarotto, M. Chierichetti, A. Poletti. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 21:12(2020 Jun 16).
Titolo: | Multiple Roles of Transforming Growth Factor Beta in Amyotrophic Lateral Sclerosis |
Autori: | CRIPPA, VALERIA (Secondo) CHIERICHETTI, MARTA (Penultimo) POLETTI, ANGELO (Ultimo) (Corresponding) |
Parole Chiave: | ALS; TGFB; motor neuron; glial cells; skeletal muscle ; SMAD |
Settore Scientifico Disciplinare: | Settore BIO/09 - Fisiologia Settore BIO/13 - Biologia Applicata |
Progetto: | From RNA to Protein toxicity in motorneuron diseases Translating molecular mechanisms into ALS risk and patient's well-being RAN translation of normal and expanded nucleotide repeat containing transcripts to neurotoxic polypetides in neurodegenerative diseases Alternative translation initiation as a novel strategy to block toxicity of the mutant Androgen Receptor in SBMA Selective translation of androgen receptor isoform A to prevent polyQ mediated toxicity in Kennedy’s disease Extracellular vescicles in the pathogenesis of frontotemporal dementia Stress granules and proteostasis in motor neurons: towards a mechanistic understanding of ALS (CureALS) Membrane-less organelle pathology in ALS: identification of causes and rescuing factors (MLOMALS) Colchicine for Amyotrophic Lateral Sclerosis: a phase II, randomized, double blind, placebo controlled, multicenter clinical trial (Co-ALS) Targeting RAN translation in ALS (Target-RAN) The interplay between the “rna/protein quality control system” and “exosomes” as a spreading mechanism in amyotrophic lateral sclerosis (EX_ALS) Extracellular vescicles in the pathogenesis of frontotemporal dementia Motor neuron degeneration in Spinal and Bulbar Muscular Atrophy: molecular approaches to counteract mutant androgen receptor neurotoxicity Ruolo protettivo della proteina HSPB8 nelle malattie del motoneurone Upregulation of HSPB8 as potential therapeutic approach in familial and sporadic ALS |
Data di pubblicazione: | 16-giu-2020 |
Rivista: | |
Centro di ricerca: | Centro Interdipartimentale di Eccellenza per le Malattie Neurodegenerative CEND |
Tipologia: | Article (author) |
Digital Object Identifier (DOI): | http://dx.doi.org/10.3390/ijms21124291 |
Appare nelle tipologie: | 01 - Articolo su periodico |
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