Ganoderma lucidum extract ameliorates MPTP-induced parkinsonism and protects dopaminergic neurons from oxidative stress via regulating mitochondrial function, autophagy, and apoptosis

Authors: Zhi-li Ren1, Chao-dong Wang1,2,3,4, Tao Wang5, Hui Ding1, Ming Zhou1, Nan Yang6, Yan-yong Liu6, Piu Chan1,2,3,4
1 Department of Neurobiology, Neurology and Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing Institute of Geriatrics, Beijing 100053, China
2 Clinical and Research Center for Parkinson’s Disease, Capital Medical University, Beijing 100053, China
3 Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing Key Laboratory for Parkinson’s Disease, Parkinson Disease Center of Beijing Institute for Brain Disorders, Beijing 100053, China
4 National Clinical Research Center for Geriatrics Disorders, Beijing 100053, China
5 National Center for ADR Monitoring, Beijing 100045, China
6 Department of Pharmacology, Institute of Basic Medical Sciences, Center of Neuroscience, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
Correspondence to: Piu Chan:,
DOI: 10.1038/s41401-018-0077-8
Received: 1 March 2018
Accepted: 14 June 2018
Advance online: 10 July 2018


Neuroprotection targeting mitochondrial dysfunction has been proposed as an important therapeutic strategy for Parkinson’s disease. Ganoderma lucidum (GL) has emerged as a novel agent that protects neurons from oxidative stress. However, the detailed mechanisms underlying GL-induced neuroprotection have not been documented. In this study, we investigated the neuroprotective effects of GL extract (GLE) and the underlying mechanisms in the classic MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced mouse model of PD. Mice were injected with MPTP to induce parkinsonism. Then the mice were administered GLE (400 mg kg−1 d−1, ig) for 4 weeks. We observed that GLE administration significantly improved locomotor performance and increased tyrosine hydroxylase expression in the substantia nigra pars compact (SNpc) of MPTP-treated mice. In in vitro study, treatment of neuroblastoma neuro-2a cells with 1-methyl-4-phenylpyridinium (MPP+, 1 mmol/L) caused mitochondrial membrane potential collapse, radical oxygen species accumulation, and ATP depletion. Application of GLE (800 μg/mL) protected neuroblastoma neuro-2a cells against MPP+ insult. Application of GLE also improved mitochondrial movement dysfunction in cultured primary mesencephalic neurons. In addition, GLE counteracted the decline in NIX (also called BNIP3L) expression and increase in the LC3-II/LC3-I ratio evoked by MPP+. Moreover, GLE reactivated MPP+-inhibited AMPK, mTOR, and ULK1. Similarly, GLE was sufficient to counteract MPP+-induced inhibition of PINK1 and Parkin expression. GLE suppressed MPP+-induced cytochrome C release and activation of caspase-3 and caspase-9. In summary, our results provide evidence that GLE ameliorates parkinsonism pathology via regulating mitochondrial function, autophagy, and apoptosis, which may involve the activation of both the AMPK/mTOR and PINK1/Parkin signaling pathway.
Keywords: ganoderma lucidum extract; parkinsonism; mitochondrial dysfunction; autophagy; apoptosis; MPTP

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