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Reduction of Lewy Body Pathology by Oral Cinnamon

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Abstract

α-Synucleinopathies in a broader sense comprise of several neurodegenerative disorders that primarily include Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). These disorders are well characterized by the accumulation of aggregated insoluble α-synuclein (α-syn) protein known as Lewy bodies. Till date no effective cure is available to reduce the burden of Lewy body. The present investigation underlines the importance of a naturally used spice and flavoring agent viz. cinnamon in reducing α-syn deposits in transgenic mice expressing mutant A53T human α-syn. Upon oral administration, cinnamon markedly reduced the level of insoluble α-syn in nigra, hippocampus and brain stem of A53T mice. We also demonstrated that sodium benzoate (NaB), a metabolite of cinnamon, a widely used food additive and a FDA-approved drug for glycine encephalopathy, was also capable of reducing α-syn deposits in A53T mice. In addition, both cinnamon and NaB treatments showed improvement in their motor and cognitive functions. Glial activation plays an important role in the pathogenesis of various neurodegenerative disorders including PD, DLB and MSA, and we found suppression of microglial and astroglial activation in the nigra of A53T mice upon cinnamon treatment. Moreover, neuroprotective proteins like DJ-1 and Parkin are known to reduce the formation of Lewy bodies in the CNS. Accordingly, we observed upregulation and/or normalization of DJ-1 and Parkin in the nigra of A53T mice by treatment with cinnamon and NaB. Together, these results highlight a new therapeutic property of cinnamon and suggest that cinnamon and NaB may be used to halt the progression of α-synucleinopathies.

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Acknowledgements

This study was supported by merit awards (1I01BX003033 and 1I01BX005002) from US Department of Veterans Affairs and a grant from NIH (NS108025). Moreover, Dr. Pahan is the recipient of a Research Career Scientist Award (1IK6 BX004982) from the Department of Veterans Affairs.

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  1. Department of Neurological Sciences, Rush University Medical Center, 1735 West Harrison St, Suite 310, Chicago, IL, 60612, USA

    Sumita Raha, Debashis Dutta, Avik Roy & Kalipada Pahan

  2. Division of Research and Development, Jesse Brown Veterans Affairs Medical Center, 820 South Damen Avenue, Chicago, IL, 60612, USA

    Kalipada Pahan

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  1. Sumita Raha
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Correspondence to Kalipada Pahan.

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Raha, S., Dutta, D., Roy, A. et al. Reduction of Lewy Body Pathology by Oral Cinnamon. J Neuroimmune Pharmacol 16, 592–608 (2021). https://doi.org/10.1007/s11481-020-09955-2

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