biostudies-literatureDe Marchi FATSDR CDC HHSNIEHS NIH HHS958-978https://www.ebi.ac.uk/biostudies/studies/S-EPMC8428677biostudies-literatureUnknown127Amyotrophic lateral sclerosis (ALS) is a debilitating and rapidly fatal neurodegenerative disease. Despite decades of research and many new insights into disease biology over the 150 years since the disease was first described, causative pathogenic mechanisms in ALS remain poorly understood, especially in sporadic cases. Our understanding of the role of the immune system in ALS pathophysiology, however, is rapidly expanding. The aim of this manuscript is to summarize the recent advances regarding the immune system involvement in ALS, with particular attention to clinical translation. We focus on the potential pathophysiologic mechanism of the immune system in ALS, discussing local and systemic factors (blood, cerebrospinal fluid, and microbiota) that influence ALS onset and progression in Neuroscience and biobehavioral reviewsInterplay between immunity and amyotrophic lateral sclerosis: Clinical impact.PMC8428677R01 ES030049R01 TS000289De Marchi FPrtenjaca NFeldman ELVan Weehaeghe DAmedei ABerry JDSakowski SANardo GBendotti CMazzini LMunitic IAronica ENiccolai EfalseInterplay between immunity and amyotrophic lateral sclerosis: Clinical impact.Amyotrophic lateral sclerosis (ALS) is a debilitating and rapidly fatal neurodegenerative disease. Despite decades of research and many new insights into disease biology over the 150 years since the disease was first described, causative pathogenic mechanisms in ALS remain poorly understood, especially in sporadic cases. Our understanding of the role of the immune system in ALS pathophysiology, however, is rapidly expanding. The aim of this manuscript is to summarize the recent advances regarding the immune system involvement in ALS, with particular attention to clinical translation. We focus on the potential pathophysiologic mechanism of the immune system in ALS, discussing local and systemic factors (blood, cerebrospinal fluid, and microbiota) that influence ALS onset and progression in 2021-01-01T00:00:00Z2021 Aug2025-04-04T22:33:05.385Z2025-02-19T03:23:57.318ZS-EPMC84286773415334410.1016/j.neubiorev.2021.06.027