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.

Graphical Abstract

广义上的 α-突触核蛋白病包括几种神经退行性疾病，主要包括帕金森病 (PD)、路易体痴呆 (DLB) 和多系统萎缩 (MSA)。这些疾病的特征在于聚集的不溶性 α-突触核蛋白 (α-syn) 蛋白（称为路易体）的积累。迄今为止，还没有有效的治疗方法来减轻路易体的负担。目前的调查强调了天然使用的香料和调味剂的重要性。肉桂可减少表达突变 A53T 人 α-syn 的转基因小鼠中的 α-syn 沉积物。口服后，肉桂显着降低了 A53T 小鼠黑质、海马和脑干中不溶性 α-syn 的水平。我们还证明了苯甲酸钠 (NaB)，一种肉桂的代谢物，一种广泛使用的食品添加剂和 FDA 批准的甘氨酸脑病药物，也能够减少 A53T 小鼠的 α-syn 沉积。此外，肉桂和 NaB 治疗均显示其运动和认知功能有所改善。胶质细胞活化在包括 PD、DLB 和 MSA 在内的各种神经退行性疾病的发病机制中起重要作用，我们发现肉桂治疗后 A53T 小鼠黑质中的小胶质细胞和星形胶质细胞活化受到抑制。此外，众所周知，DJ-1 和 Parkin 等神经保护蛋白可以减少 CNS 中路易体的形成。因此，我们通过肉桂和 NaB 处理观察到 A53T 小鼠黑质中 DJ-1 和 Parkin 的上调和/或正常化。一起，

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