The amyotrophic lateral sclerosis exposome: recent advances and future directions.
Nat Rev Neurol
; 19(10): 617-634, 2023 10.
Article
em En
| MEDLINE
| ID: mdl-37709948
ABSTRACT
Amyotrophic lateral sclerosis (ALS) is a fatal disease of motor neuron degeneration with typical survival of only 2-5 years from diagnosis. The causes of ALS are multifactorial known genetic mutations account for only around 70% of cases of familial ALS and 15% of sporadic cases, and heritability estimates range from 8% to 61%, indicating additional causes beyond genetics. Consequently, interest has grown in environmental contributions to ALS risk and progression. The gene-time-environment hypothesis posits that ALS onset occurs through an interaction of genes with environmental exposures during ageing. An alternative hypothesis, the multistep model of ALS, suggests that several hits, at least some of which could be environmental, are required to trigger disease onset, even in the presence of highly penetrant ALS-associated mutations. Studies have sought to characterize the ALS exposome - the lifetime accumulation of environmental exposures that increase disease risk and affect progression. Identifying the full scope of environmental toxicants that enhance ALS risk raises the prospect of preventing disease by eliminating or mitigating exposures. In this Review, we summarize the evidence for an ALS exposome, discussing the strengths and limitations of epidemiological studies that have identified contributions from various sources. We also consider potential mechanisms of exposure-mediated toxicity and suggest future directions for ALS exposome research.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Expossoma
/
Esclerose Lateral Amiotrófica
Tipo de estudo:
Etiology_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article