Genetic architecture of amyotrophic lateral sclerosis: a comprehensive review

Lamei Yuan; Yuewen Yang; Yi Guo; Hao Deng

doi:10.1016/j.jgg.2025.05.008

Genetic architecture of amyotrophic lateral sclerosis: a comprehensive review

doi: 10.1016/j.jgg.2025.05.008

Lamei Yuan^a,b,c,d, ,,
Yuewen Yang^a,
Yi Guo^e,
Hao Deng^a,b,c,d, ,

a. Research Center of Medical Experimental Technology, the Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China;
b. Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China;
c. Disease Genome Research Center, Central South University, Changsha, Hunan 410013, China;
d. Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China;
e. Department of Medical Information, School of Life Sciences, Central South University, Changsha, Hunan 410013, China

基金项目:

This work was funded by National Natural Science Foundation of China (81800219), Natural Science Foundation of Hunan Province (2023JJ30715), Scientific Research Project of Hunan Provincial Health Commission (A202303018385 and B202303078399), Health Research Project of Hunan Provincial Health Commission (W20243024), Province-level College Students’ Innovative Training Plan Program (S202310533352), Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hospital of Central South University (YX202109), Sublimation Scholars Project of Central South University, and Distinguished Professor of the Lotus Scholars Award Program of Hunan Province, China.

详细信息

通讯作者:
Lamei Yuan,E-mail:yuanlamei229@163.com

Hao Deng,E-mail:hdeng008@163.com

计量
- 文章访问数: 5
- HTML全文浏览量: 3
- PDF下载量: 0
- 被引次数: 0
出版历程
- 收稿日期: 2025-02-24
- 录用日期: 2025-05-21
- 修回日期: 2025-05-16
- 网络出版日期: 2025-07-11

Genetic architecture of amyotrophic lateral sclerosis: a comprehensive review

Lamei Yuan^{a,b,c,d
, ,},
Yuewen Yang^a,
Yi Guo^e,
Hao Deng^{a,b,c,d
, ,}

a. Research Center of Medical Experimental Technology, the Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China;
b. Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China;
c. Disease Genome Research Center, Central South University, Changsha, Hunan 410013, China;
d. Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China;
e. Department of Medical Information, School of Life Sciences, Central South University, Changsha, Hunan 410013, China

Funds:

摘要

摘要:
Amyotrophic lateral sclerosis (ALS), one of the most prevalent neurodegenerative disorders, is pathologically characterized by the progressive degeneration of both upper and lower motor neurons, leading to muscle weakness, paralysis, and death within 2-4 years post-diagnosis. ALS is categorized into familial ALS (FALS) and sporadic ALS, with FALS accounting for approximately 10% of ALS cases. As a genetically heterogeneous disease, ALS exhibits diverse inheritance patterns, including autosomal dominant, autosomal recessive, and X-linked transmission, and genetic factors play pivotal roles in disease pathogenesis. To date, at least 34 disease-causing loci and 32 genes for ALS have been identified. The investigations of mutant protein products and the establishment of animal models have unraveled potential pathogenic pathways, offering insights into the mechanisms of neurodegeneration in ALS. This review focuses on ALS clinical characteristics, neuropathological features, causative loci/genes, genetic susceptibility factors, animal models, and pathogenic mechanisms, with particular attention to recent advances in genetic findings and pathogenic pathways of ALS. Elucidation of the genetic basis of ALS could provide the scientific foundation for personalized treatments to address this recalcitrant disease.
- Amyotrophic lateral sclerosis /
- Neurodegenerative disease /
- Genetics /
- Variants /
- Pathogenic pathway /
- Animal models
Abstract:
Amyotrophic lateral sclerosis (ALS), one of the most prevalent neurodegenerative disorders, is pathologically characterized by the progressive degeneration of both upper and lower motor neurons, leading to muscle weakness, paralysis, and death within 2-4 years post-diagnosis. ALS is categorized into familial ALS (FALS) and sporadic ALS, with FALS accounting for approximately 10% of ALS cases. As a genetically heterogeneous disease, ALS exhibits diverse inheritance patterns, including autosomal dominant, autosomal recessive, and X-linked transmission, and genetic factors play pivotal roles in disease pathogenesis. To date, at least 34 disease-causing loci and 32 genes for ALS have been identified. The investigations of mutant protein products and the establishment of animal models have unraveled potential pathogenic pathways, offering insights into the mechanisms of neurodegeneration in ALS. This review focuses on ALS clinical characteristics, neuropathological features, causative loci/genes, genetic susceptibility factors, animal models, and pathogenic mechanisms, with particular attention to recent advances in genetic findings and pathogenic pathways of ALS. Elucidation of the genetic basis of ALS could provide the scientific foundation for personalized treatments to address this recalcitrant disease.
- Amyotrophic lateral sclerosis /
- Neurodegenerative disease /
- Genetics /
- Variants /
- Pathogenic pathway /
- Animal models