Linalool as a therapeutic agent in neurodegeneration

Neurodegenerative diseases are hereditary and sporadic, characterized by progressive nervous system dysfunction, including the Alzheimer's disease (AD) and other ageing-related progressive neurodegenerative disorders, as stroke. Ischemic stroke is frequently caused by a blood clot that occlude blood vessels in the brain ^[1]. Several kind of treatments have been tested for blocking or delaying the onset of those diseases, without successful. Dietary life style and natural products have a big potential in the current scientific focus. In the present study, we evaluated the Linalool effect in an in vitro model using a neuronal excitotoxicity model by glutamate (125µM) and an in in vivo global ischemia model in Wistar rats. Linalool was gaven by oral via at 25 mg/kg every 24 hours for 1 month, after behavioral tests were realized. Our in vitro results showed more than 50% protection by Linalool's (100nm) pre-treatment and post-treatment. Besides, animals Linalool-treated had a neurological recovery faster than untreated animals at 24 and 48 hours post-ischemia, accompained with a better performance in the Rotarod and inclined plane tests. Although, no differences were found in learning test, relearning tasks were improved in animals treated with Linalool compared with vehicle-ischemic group. Findings suggest the neuroprotection action by Linalool in ischemic rats, confirming our previous studies developed where aged triple transgenic AD model mice (21 – 24 months old) treated with Linalool during 3 months showed a significant reduction of extracellular β-amyloidosis, tauopathy, astrogliosis and microgliosis in the hippocampus and amygdala. In addition, they had a significant improvement in the learning and spatial memory tasks and greater risk assessment behavior ^[2]. Together, our findings suggest the natural product Linalool as a potential therapeutic candidate for preclinical studies of prevention and future translational studies in Neurodegenerative diseases.

Acknowledgements: We would like to thank to the Cellular and Molecular Neurobiology Area, Group of Neuroscience, University of Antioquia (UdeA); Group of Bioactive Substances UdeA; Professor Jose Ramirez, Group of Immunomodulation, UdeA; Professor Marisol Lamprea Neuroscience Lab at National University of Colombia for their scientific and technical support during the experiments. This research was funded by grant from COLCIENCIAS 11565740581 (GPC-G), CODI Universidad de Antioquia.

Keywords: Linalool, motor and cognitive function, Ischemic stroke, Alzheimer's disease.

References:

[1] Lewerenz J, Maher P. Chronic Glutamate Toxicity in Neurodegenerative Diseases-What is the Evidence?. Front Neuroscience 2015; 9: 1 – 20

[2] Sabogal-Guaqueta A, Osorio E, Cardona Gomez G. Linalool reverses neuropathological and behavioral impairments in old triple transgenic Alzheimer's mice Linalool. Neuropharmacology 2016; 102:111 – 120

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