Vitamin B12 is identified as the inhibitor of a key enzyme in hereditary Parkinson's disease

Date: April 4, 2019 Source: University of the Basque Country Summary: Parkinson's is the most common, chronic neurodegenerative movement disorder affecting 1% of the global population over seventy years of age. Right now, there is no cure for this disease and the available treatments focus on addressing its symptoms but not its progression.

Parkinson's is the most common, chronic neurodegenerative movement disorder affecting 1% of the global population over seventy years of age. Right now, there is no cure for this disease and the available treatments focus on addressing its symptoms but not its progression.

Although most cases of Parkinson's are sporadic, the inheritable variants of the disease are mainly associated with mutations of the gene that encodes the LRRK2 enzyme. In 2004 an international research team, in which researchers from the Basque Country participated, established the link between one of the mutations in this enzyme and patients diagnosed with the disease.

So the LRRK2 enzyme, which is also known internationally by the name "dardarina," the Basque word that means tremor, has become one of the most attractive therapeutic targets for developing new drugs to combat inheritable Parkinson's. Neurotoxicity, or the pathogenic effects as a whole associated with LRRK2, is mainly due to the fact that pathogenic mutations increase the kinase activity of this enzyme, which has prompted an international race to develop inhibitors. Right now, specific, powerful inhibitors of the kinase activity of LRRK2 do in fact exist. Yet many of them cause undesirable side effects or produce very unclear clinical results.

This research conducted by Iban Ubarretxena, the Ikerbasque researcher and director of the Biofisika Institute (mixed centre of the CSIC-Spanish National Research Council and the UPV/EHU-University of the Basque Country) at the UPV/EHU's Science Park (Leioa-Erandio Area), together with an international research team, has revealed that AdoCbl, one of the active forms of vitamin B12, acts as an inhibitor of the kinase activity of LRRK2 in cultured cells and brain tissue. It also significantly prevents the neurotoxicity of the LRRK2 variants associated with Parkinson's in cultured cells of primary rodents, as well as in various genetically modified models used to study this disease. The results of the research have been published in the journal Cell Research.

So according to the study, vitamin B12 has turned out to be a new class of modulator of the kinase activity of LRRK2, which, as Iban Ubarretxena pointed out, "constitutes a huge step forward because it is a neuroprotective vitamin in animal models and has a mechanism unlike that of currently existing inhibitors. So it could be used as a basis to develop new therapies to combat hereditary Parkinson's associated with pathogenic variants of the LRRK2 enzyme."

Story Source:

Materials provided by University of the Basque Country. Note: Content may be edited for style and length.

Journal Reference:

Adam Schaffner, Xianting Li, Yacob Gomez-Llorente, Emmanouela Leandrou, Anna Memou, Nicolina Clemente, Chen Yao, Farinaz Afsari, Lianteng Zhi, Nina Pan, Keita Morohashi, Xiaoluan Hua, Ming-Ming Zhou, Chunyu Wang, Hui Zhang, Shu G. Chen, Christopher J. Elliott, Hardy Rideout, Iban Ubarretxena-Belandia, Zhenyu Yue. Vitamin B12 modulates Parkinson’s disease LRRK2 kinase activity through allosteric regulation and confers neuroprotection. Cell Research, 2019; 29 (4): 313 DOI: 10.1038/s41422-019-0153-8

Cite This Page:

MLA

APA

Chicago

University of the Basque Country. "Vitamin B12 is identified as the inhibitor of a key enzyme in hereditary Parkinson's disease." ScienceDaily. ScienceDaily, 4 April 2019. <www.sciencedaily.com/releases/2019/04/190404124818.htm>.