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Neurosci Lett. 2019 Jan 18;690:145-150. doi: 10.1016/j.neulet.2018.10.020. Epub 2018 Oct 11.

Synphilin-1 has neuroprotective effects on MPP+-induced Parkinson's disease model cells by inhibiting ROS production and apoptosis.

Author information

1
Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Minami-ku Kasumi, Hiroshima, 734-8551, Japan.
2
Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Minami-ku Kasumi, Hiroshima, 734-8551, Japan. Electronic address: yachtz@hiroshima-u.ac.jp.
3
Department of Neurology, NHO Kure Medical Center, 3-1 Aoyama-cho, Kure, Hiroshima, 737-0023, Japan.
4
Department of Internal Medicine, Oyamada Memorial Spa Hospital, 5538-1 Yamada-cho, Yokkaichi, Mie, 512-1111, Japan.
5
Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Minami-ku Kasumi, Hiroshima, 734-8551, Japan; Sakai City Medical Center, Sakai City Hospital Organization, 1-1-1 Ebaraji-cho Nishi-ku, Sakai, Osaka, 593-8304, Japan.

Abstract

Synphilin-1, a cytoplasmic protein, interacts with α-synuclein which is one of the main constituents of Lewy bodies and plays an important role in the pathology of Parkinson's disease (PD), in neurons. This interaction indicates that synphilin-1 may also play a central role in PD. However, the biological functions of synphilin-1 are not fully understood, and whether synphilin-1 is neurotoxic or neuroprotective remains controversial. This study examined the function of synphilin-1 in a PD model in vitro. We used an inhibitor of mitochondrial complex I, 1-methyl-4-phenylpyridinium (MPP+). We established human neuroblastoma SH-SY5Y cell lines that stably expressed human synphilin-1. We found that overexpression of synphilin-1 increased SH-SY5Y cell viability after MPP+ treatment. We further found that synphilin-1 significantly suppressed apoptotic changes in nuclei, including nuclear condensation and fragmentation, after MPP+ treatment. We showed that synphilin-1 significantly decreased MPP+-induced cleaved caspase-3 and cleaved poly-ADP-ribose polymerase levels by using western blotting. Production of reactive oxygen species (ROS) induced by MPP+ was significantly reduced in cells expressing synphilin-1 compared to those expressing empty vector. Synphilin-1 inhibited MPP+-induced cytochrome c release from mitochondria into the cytosol. These data suggested that synphilin-1 may function to protect against dopaminergic cell death by preserving mitochondrial function and inhibiting early steps in the intrinsic apoptotic pathway. Taken together, our results indicated that synphilin-1 may play neuroprotective roles in PD pathogenesis by inhibiting ROS production and apoptosis.

KEYWORDS:

Apoptosis; Dopaminergic neurodegeneration; MPP(+); Parkinson’s disease; synphilin-1

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