The National Research Foundation of Korea announced on the 12th that a joint research team led by Professor Kim Seung-hyun of Hanyang University and Senior Researcher Nam Min-yeop of the Korea Brain Research Institute has newly identified the genetic mechanisms that cause amyotrophic lateral sclerosis (ALS).
ALS is a degenerative neurological disease characterized by the progressive loss of motor neurons, leading to muscle paralysis. The process of the disease is not clearly understood, and there is no fundamental treatment available, making it difficult to treat. Recently, the NEK1 gene has emerged as one of the risk genes for ALS, but how mutations in this gene lead to the disease has not been specifically clarified.
The research team analyzed the genetic information of 920 Korean ALS patients and discovered mutations in the NEK1 gene in 2.5% of the patients. They confirmed that patients with this mutation experience a faster disease progression and a shorter survival period.
Analysis using patient cells revealed that the NEK1 mutation inhibits the formation of cilia, which act as antennas for the cell, leading to the disruption of intracellular calcium homeostasis, mitochondrial dysfunction, and failure to repair deoxyribonucleic acid (DNA) damage.
The research team also confirmed that using histone deacetylase 6 (HDAC6) inhibitors can recover cilia damage and mitochondrial abnormalities caused by NEK1 mutations, as well as restore cell cycle changes and cell death. This indicates the potential for HDAC6 inhibitors to be used as a treatment for ALS.
The research team noted, "The results of this study can be applied to the development of next-generation ALS treatments and patient-customized clinical designs," adding, "It is necessary to verify whether the mechanism is reproduced in actual patient brain tissues and whether HDAC6 inhibitors are clinically effective."
The research findings were published in the international journal of neuroscience, "Molecular neurodegeneration," on the 20th of last month.
References
Molecular neurodegeneration (2025), DOI: https://doi.org/10.1186/s13024-025-00848-7