Vitamin B12 may have neuroprotective role to combat hereditary Parkinson's disease

Vitamin B12 may have a neuroprotective role to combat hereditary Parkinson's disease. The results of the research have been published in the prestigious journal Cell Research.

Parkinson's is the most common, chronic neurodegenerative movement disorder which has no cure. It affects 1% of the elderly population over seventy years of age globally.

Parkinsonism is the umbrella term given to a group of conditions that feature Parkinson’s-type symptoms: tremor, the stiffness of muscles and slowness of movement (bradykinesia). The majority of patients (around 80-85 percent) diagnosed with Parkinson’s disease have what is called primary parkinsonism or idiopathic Parkinson’s disease.

The remaining types of Parkinson’s are termed secondary or atypical parkinsonism.

There are inheritable variants of the disease also which 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.

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".

For more details click on the link: http://dx.doi.org/10.1038/s41422-019-0153-8