LINGO1, the leucine-rich repeat and Ig domain containing 1 gene, is a transmembrane protein. It has been hypothesized to be a regulatory subunit of large conductance, Ca2+-activated potassium (BK) channels [1]. Its up-regulation has been associated with potential pathological responses to neurodegenerative processes [3].

Genetic variations in LINGO1 have been linked to essential tremor (ET) and Parkinson's disease (PD). Some studies found LINGO1 protein levels increased in the cerebellum of ET and PD patients, especially with longer disease duration in ET [3]. In a South Indian family with dystonic tremor, an additional LINGO1 gene copy was identified, suggesting its causal role in tremor disorders [2]. One study in aged mice showed that increased Lingo1 expression in hippocampal neurons after surgery led to cognitive impairment via activation of the RhoA/ROCK1 signaling pathway and inhibition of the EGFR/PI3K/Akt pathway [4]. However, some studies failed to find an association between LINGO1 SNPs and PD in certain populations [5,6].

In conclusion, LINGO1 may play a role in the pathogenesis of movement disorders like ET and PD, as well as in cognitive dysfunction after surgery in aged mice. Studies on LINGO1, especially through in vivo models, contribute to understanding its role in these disease conditions, potentially providing insights for developing new treatment strategies.

References:

1. Dudem, Srikanth, Large, Roddy J, Kulkarni, Shruti, Perrino, Brian A, Hollywood, Mark A. 2020. LINGO1 is a regulatory subunit of large conductance, Ca2+-activated potassium channels. In Proceedings of the National Academy of Sciences of the United States of America, 117, 2194-2200. doi:10.1073/pnas.1916715117. https://pubmed.ncbi.nlm.nih.gov/31932443/

2. Alakbarzade, Vafa, Iype, Thomas, Chioza, Barry A, Warner, Thomas T, Crosby, Andrew H. 2019. Copy number variation of LINGO1 in familial dystonic tremor. In Neurology. Genetics, 5, e307. doi:10.1212/NXG.0000000000000307. https://pubmed.ncbi.nlm.nih.gov/30842974/

3. Delay, Charlotte, Tremblay, Cyntia, Brochu, Elodie, Rajput, Alex, Calon, Frédéric. 2014. Increased LINGO1 in the cerebellum of essential tremor patients. In Movement disorders : official journal of the Movement Disorder Society, 29, 1637-47. doi:10.1002/mds.25819. https://pubmed.ncbi.nlm.nih.gov/24531928/

4. Liu, Changliang, Zhang, Changteng, Chen, Ling, Liu, Jin, Chen, Chan. 2025. Lingo1 in the hippocampus contributes to cognitive dysfunction after anesthesia and surgery in aged mice. In International journal of biological sciences, 21, 595-613. doi:10.7150/ijbs.98376. https://pubmed.ncbi.nlm.nih.gov/39781463/

5. Klebe, Stephan, Thier, Sandra, Lorenz, Delia, Deuschl, Günther, Kuhlenbäumer, Gregor. . LINGO1 is not associated with Parkinson's disease in German patients. In American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 153B, 1173-8. doi:10.1002/ajmg.b.31085. https://pubmed.ncbi.nlm.nih.gov/20468067/

6. Guo, Yi, Jankovic, Joseph, Song, Zhi, Luo, Ziqiang, Deng, Hao. 2010. LINGO1 rs9652490 variant in Parkinson disease patients. In Neuroscience letters, 487, 174-6. doi:10.1016/j.neulet.2010.10.016. https://pubmed.ncbi.nlm.nih.gov/20951767/