AUTHOR=Zampatti Stefania , Peconi Cristina , Campopiano Rosa , Gambardella Stefano , Caltagirone Carlo , Giardina Emiliano 

TITLE=C9orf72-Related Neurodegenerative Diseases: From Clinical Diagnosis to Therapeutic Strategies

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=14

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.907122

DOI=10.3389/fnagi.2022.907122

ISSN=1663-4365

ABSTRACT=<p>Hexanucleotide expansion in <italic>C9orf72</italic> has been related to several phenotypes to date, complicating the clinical recognition of these neurodegenerative disorders. An early diagnosis can improve the management of patients, promoting early administration of therapeutic supportive strategies. Here, we report known clinical presentations of <italic>C9orf72</italic>-related neurodegenerative disorders, pointing out suggestive phenotypes that can benefit the genetic characterization of patients. Considering the high variability of <italic>C9orf72</italic>-related disorder, frequent and rare manifestations are described, with detailed clinical, instrumental evaluation, and supportive therapeutical approaches. Furthermore, to improve the understanding of molecular pathways of the disease and potential therapeutical targets, a detailed description of the cellular mechanisms related to the pathological effect of <italic>C9orf72</italic> is reported. New promising therapeutical strategies and ongoing studies are reported highlighting their molecular role in cellular pathological pathways of <italic>C9orf72</italic>. These therapeutic approaches are particularly promising because they seem to stop the disease before neuronal damage. The knowledge of clinical and molecular features of <italic>C9orf72</italic>-related neurodegenerative disorders improves the therapeutical application of known strategies and will lay the basis for the development of new potential therapies.</p>