RIT2基因,也称为Ras-like without CAAX 2,编码一种GTP结合蛋白,属于Ras超家族成员。该基因在多种重要的细胞功能中发挥作用,如细胞分化、存活和信号传导。RIT2蛋白在神经系统中尤为丰富,其表达与多种神经退行性疾病和神经精神疾病相关。
近年来,越来越多的研究揭示了RIT2基因在神经系统疾病中的重要作用。例如,Daneshmandpour等人发现,RIT2基因变异与多种神经退行性疾病和神经精神疾病相关,包括帕金森病、精神分裂症和自闭症[1]。此外,Hamedani等人研究发现,RIT2基因的SNP rs16976358与自闭症谱系障碍(ASD)的易感性相关[2]。Emamalizadeh等人发现,RIT2基因的SNP rs12456492与伊朗人群中帕金森病的易感性相关[3]。Wang等人通过单细胞转录组分析发现,RIT2基因在帕金森病中表现出独特的表达模式,并参与了自噬-溶酶体途径的调控[4]。此外,Emamalizadeh等人还发现,RIT2基因的SNP rs12456492与帕金森病和特发性震颤相关,而SNP rs16976358与自闭症、精神分裂症和双相情感障碍相关[5]。Gao等人研究发现,RIT2基因通过调节自噬-溶酶体途径,对帕金森病中的α-突触核蛋白病理学具有保护作用[6]。Nie等人研究发现,RIT2基因的SNP rs12456492与中国汉族人群中帕金森病的易感性相关[7]。Rosoff等人研究发现,RIT2基因的表达与吸烟行为相关,可能参与了吸烟相关的生物学过程[8]。Sweeney等人研究发现,RIT2基因在多巴胺能神经元中具有性别特异性的功能,可能参与了急性可卡因反应和纹状体功能[9]。Wang等人通过meta分析发现,RIT2基因的SNP rs16976358与亚洲人群中自闭症的易感性相关[10]。
综上所述,RIT2基因在神经系统中发挥重要作用,与多种神经退行性疾病和神经精神疾病相关。RIT2基因的表达和功能调控可能为这些疾病的治疗和预防提供新的思路和策略。未来需要进一步深入研究RIT2基因在神经系统疾病中的具体作用机制,以及与其他基因和蛋白质的相互作用,为相关疾病的治疗和预防提供更深入的理解和更有效的策略。
参考文献:
1. Daneshmandpour, Yousef, Darvish, Hossein, Emamalizadeh, Babak. 2018. RIT2: responsible and susceptible gene for neurological and psychiatric disorders. In Molecular genetics and genomics : MGG, 293, 785-792. doi:10.1007/s00438-018-1451-4. https://pubmed.ncbi.nlm.nih.gov/29860660/
2. Hamedani, Shima Yazdandoost, Gharesouran, Jalal, Noroozi, Rezvan, Ghafouri-Fard, Soudeh, Taheri, Mohammad. 2017. Ras-like without CAAX 2 (RIT2): a susceptibility gene for autism spectrum disorder. In Metabolic brain disease, 32, 751-755. doi:10.1007/s11011-017-9969-4. https://pubmed.ncbi.nlm.nih.gov/28190241/
3. Emamalizadeh, Babak, Movafagh, Abolfazl, Akbari, Mojdeh, Mirfakhraie, Reza, Darvish, Hossein. 2014. RIT2, a susceptibility gene for Parkinson's disease in Iranian population. In Neurobiology of aging, 35, e27-e28. doi:10.1016/j.neurobiolaging.2014.07.013. https://pubmed.ncbi.nlm.nih.gov/25146456/
4. Wang, Qian, Wang, Minghui, Choi, Insup, Zhang, Bin, Yue, Zhenyu. 2024. Molecular profiling of human substantia nigra identifies diverse neuron types associated with vulnerability in Parkinson's disease. In Science advances, 10, eadi8287. doi:10.1126/sciadv.adi8287. https://pubmed.ncbi.nlm.nih.gov/38198537/
5. Emamalizadeh, Babak, Jamshidi, Javad, Movafagh, Abolfazl, Atakhorrami, Minoo, Darvish, Hossein. 2016. RIT2 Polymorphisms: Is There a Differential Association? In Molecular neurobiology, 54, 2234-2240. doi:10.1007/s12035-016-9815-4. https://pubmed.ncbi.nlm.nih.gov/26941103/
6. Gao, Andy Y L, Montagna, Daniel R, Hirst, Warren D, Temkin, Paul A. 2024. RIT2 regulates autophagy lysosomal pathway induction and protects against α-synuclein pathology in a cellular model of Parkinson's disease. In Neurobiology of disease, 199, 106568. doi:10.1016/j.nbd.2024.106568. https://pubmed.ncbi.nlm.nih.gov/38885848/
7. Nie, Kun, Feng, Shu-jun, Tang, Hong-mei, Zhang, Yu-hu, Wang, Li-juan. 2014. RIT2 polymorphism is associated with Parkinson's disease in a Han Chinese population. In Neurobiology of aging, 36, 1603.e15-7. doi:10.1016/j.neurobiolaging.2014.10.013. https://pubmed.ncbi.nlm.nih.gov/25457028/
8. Rosoff, Daniel B, Hamandi, Ali M, Bell, Andrew S, Wagner, Josephin, Lohoff, Falk W. . Major Psychiatric Disorders, Substance Use Behaviors, and Longevity. In JAMA psychiatry, 81, 889-901. doi:10.1001/jamapsychiatry.2024.1429. https://pubmed.ncbi.nlm.nih.gov/38888899/
9. Sweeney, Carolyn G, Kearney, Patrick J, Fagan, Rita R, Martin, Gilles E, Melikian, Haley E. 2019. Conditional, inducible gene silencing in dopamine neurons reveals a sex-specific role for Rit2 GTPase in acute cocaine response and striatal function. In Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 45, 384-393. doi:10.1038/s41386-019-0457-x. https://pubmed.ncbi.nlm.nih.gov/31277075/
10. Wang, Jing, Wei, Shoupeng, Zhang, Jin, Wang, Hu. 2023. Association between RIT2 rs16976358 Polymorphism and Autism Spectrum Disorder in Asian Populations: A Meta-analysis. In BioMed research international, 2023, 8886927. doi:10.1155/2023/8886927. https://pubmed.ncbi.nlm.nih.gov/36820223/