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Ganoderma lucidum extract ameliorates MPTP-induced parkinsonism and protects dopaminergic neurons from oxidative stress via regulating mitochondrial function, autophagy, and apoptosis.
- Source :
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Acta pharmacologica Sinica [Acta Pharmacol Sin] 2019 Apr; Vol. 40 (4), pp. 441-450. Date of Electronic Publication: 2018 Jul 10. - Publication Year :
- 2019
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Abstract
- 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 <superscript>-1</superscript> d <superscript>-1</superscript> , 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 <superscript>+</superscript> , 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 <superscript>+</superscript> 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 <superscript>+</superscript> . Moreover, GLE reactivated MPP <superscript>+</superscript> -inhibited AMPK, mTOR, and ULK1. Similarly, GLE was sufficient to counteract MPP <superscript>+</superscript> -induced inhibition of PINK1 and Parkin expression. GLE suppressed MPP <superscript>+</superscript> -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.
- Subjects :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Animals
Biological Products chemistry
Biological Products isolation & purification
Disease Models, Animal
Dopaminergic Neurons metabolism
Male
Mice
Mice, Inbred C57BL
Mitochondria metabolism
Neuroprotective Agents chemistry
Neuroprotective Agents isolation & purification
Oxidative Stress drug effects
Parkinsonian Disorders chemically induced
Apoptosis drug effects
Biological Products pharmacology
Dopaminergic Neurons drug effects
Mitochondria drug effects
Neuroprotective Agents pharmacology
Parkinsonian Disorders prevention & control
Reishi chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1745-7254
- Volume :
- 40
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Acta pharmacologica Sinica
- Publication Type :
- Academic Journal
- Accession number :
- 29991712
- Full Text :
- https://doi.org/10.1038/s41401-018-0077-8