Kaemperfol Protects Dopaminergic Neurons by Promoting mTOR-Mediated Autophagy in Parkinson's Disease Models

Abstract

We previously showed that kaempferol (KAE) could exert neuroprotective effects against PD. It has been demonstrated that abnormal autophagy plays a key role in the development of PD. Mitochondrial dysfunction, involved in the development of PD, can damage dopaminergic neurons. Whether the protective effects of KAE were exerted via regulating autophagy remains largely undefined, however. This study aimed to investigate whether KAE could protect dopaminergic neurons via autophagy and the underlying mechanisms using a MPTP/MPP⁺-stimulated PD model. Cell viability was detected by cell counting kit-8 (CCK-8) assay, and protein levels of autophagy mediators along with mTOR signaling pathway molecules were investigated by immunohistochemistry and Western blot analyses. The results showed that KAE could ameliorate the behavioral impairments of mice, reduce the loss of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra pars compacta, and reduce α-synuclein (α-syn) levels. Furthermore, KAE upregulated levels of autophagy effector protein of Beclin-1 and autophagy microtubule associated protein of light chain 3 (LC3) in the substantia nigra (SN) while rescuing mitochondrial integrity, and downregulated levels of ubiquitin binding protein p62 and cleaved caspase-3, probably by decreasing the mammalian target of rapamycin (mTOR) signaling pathway. Further in vitro experiments demonstrated similar results. In conclusion, KAE exerts neuroprotective effects against PD potentially by promoting autophagy via inhibiting the mTOR signaling pathway.

Keywords: Autophagy; Kaempferol; Parkinson’s disease; mTOR signaling pathway.