SEMINAR

Parkinson’s disease and α-synuclein

Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting ~1% of people over the age of 65. Neuropathological hallmarks of PD are prominent loss of dopaminergic (DA) neurons in the substantia nigra and formation of intraneuronal protein inclusions termed Lewy bodies, composed mainly of α-synuclein (αSyn). Missense mutations in αSyn gene giving rise to production of degradation-resistant mutant proteins or multiplication of wild-type αSyn gene allele can cause rare inherited forms of PD. Therefore, the existence of abnormally high amount of αSyn protein is considered responsible for the DA neuronal death in PD. αSyn is a neuronal protein of 140-amino-acids and normally localized to presynaptic terminals. The exact physiological function of αSyn remains yet defined, but several works have implicated its role in dopamine biosynthesis, synaptic plasticity, and vesicle dynamics. I will introduce and discuss about the measurement of αSyn by HANABI (HANdai Amyloid Burst Inducer) system to diagnose the patients with PD collaborated with Dr. Goto.

BIOGRAPHY

Dr. Mochizuki is currently Professor and Chair of the Department of Neurology at Osaka University in Osaka, Japan. Prior to his present position, he served as Professor and Chair of Neurology at Kitasato University in Kanagawa, Japan. He obtained his MD and PhD degrees from Juntendo University in Tokyo, and his neurology residency at Juntendo University (1985-1987) and at Tokyo Metropolitan Neurological Hospital (1987-1989). He then completed a postdoctoral fellowship in the Developmental and Metabolic Neurology Branch of NINDS / NIH in Bethesda, Maryland under the tutelage of Roscoe Brady (1996-1998). He returned to Japan to serve on the faculty of Neurology at Juntendo University for eleven years, rose through the academic ranks until his appointment as Chairman first at Kitasato University (2009-2011) and now at Osaka University　(2011-).

Honours, Awards and Recognition:
Best Research Award, 1st Asia & Oceania Parkinson’s disease Movement Disorder Congress
Award of an alumni association in Juntendo Univeristy
Narabayashi　Award in Japan Neurological Association

Professional interests:
Parkinson’s Disease, Movement Disorders, Gene Therapy

Publications:
100 + Peer reviewed scientific papers, 12 book chapters

Fellowships and Memberships:
Executive committee of Movement Disorder Society, Japan
Member of International Movement Disorder Society,
Japan Neurological Association: PR Committee,
Member of Japan Society for Gene Therapy, Committee,
Member of American Society for Experimantal, Neurotheraputics, Development Committee,
Corresponding Member of American Neurological Association

Research interests:

Professor Mochizuki’s research interest is Parkinson’s disease with a focus on its pathogenesis using neurochemical, molecular and cell biologic studies as well as novel therapeutic approaches using gene therapy. To date, he has authored 80 original articles and 25 reviews and book chapters. In 2005, he published a paper in the Annals of Neurology describing his innovative discovery of possible neurogenesis in the substantia nigra of Parkinson’s disease affected brains. This provided a rationale for the future development of potential therapeutic strategies aimed at up-regulating neurogenesis in this brain region. Among his other seminal contributions to the literature includes the pioneering discovery of apoptotic changes in Parkinson’s disease brains, a finding subsequently confirmed by several other groups. In a publication in the Proceedings of the National Academy of Sciences, he also demonstrated that the expression of Apaf-1-dominant negative mutant in the substantia nigra inhibits apoptotic cell death in the mouse MPTP model of Parkinson’s disease. His more recent efforts focus on the development of gene therapy for the disease to deliver parkin using AAV vector. He has already demonstrated the feasibility and efficacy of this approach in a chronic MPTP mouse model. Professor Mochizuki’s research has been continuously funded by various Japanese funding agencies including the Ministry of Education, Culture, Sports, Science & Technology, the National Institute of Biomedical Innovation, and the Mitusi Life Social Welfare Foundation.

Selected publications:

1. Mochizuki H, Goto K, Mori H, Mizuno Y, Histochemical detection of apoptosis in Parkinson's disease, J Neurol Sci, 137, 120-123, 1996.
2. Mochizuki H, Schwartz JP, Tanaka K, Brady RO, Reiser J, High-titer HIV-1-based vector systems for gene delivery into nondividing cells, J Virol, 72, 8873-8883, 1998.
3. Mochizuki H, Hayakawa H, Migita M, Shibata M, Tanaka R, Suzuki A, Shimo-Nakanishi Y, Urabe T, Yamada M, Tamayose K, Shimada T, Miura M and Mizuno Y, An AAV-derived Apaf-1 dominant negative inhibitor prevents MPTP toxicity as anti- apoptotic gene therapy for Parkinson’s disease, Proc Natl Acad Sci USA, 98, 10918-10923, 2001.
4. Naito S, Mochizuki H, Yasuda T, Mizuno Y, Furusaka M, Ikeda S, Adachi T, Shimizu H, Suzuki J, Fujiwara S, Okada T, Nishikawa K, Aoki S, Wada K, Characterization of multimetric variants of ubiquitin carboxyl-terminal Hydrolase L1 in water by small-angle neutron scattering, Biochem Biophys Res Commun, 339, 717-725, 2006.
5. Nakata Y, Yasuda T, Fukaya M, Yamadori S, Itakura M, Nihira T, Hayakawa H, Kawakami A, Nagai M, Sakagami H, Miyake K, Takahashi M, Mizuno Y, Mochizuki H, Accumulation of -synuclein triggered by presynaptic dysfunction. J Neurosci 2012 Nov 28;32(48):17186-96.
6. Ohta E, Nihira T, Uchino A, Imaizumi Y, Okada Y, Akamatsu W, Takahashi K, Hayakawa H, Nagai M, Ohyama M, Ryo M, Ogino M, Murayama S, Takashima A, Nishiyama K, Mizuno Y, Mochizuki H, Obata F, Okano HI2020T mutant LRRK2 iPSC-derived neurons in the Sagamihara family exhibit increased Tau phosphorylation through the AKT/GSK-3β signaling pathway.Hum Mol Genet. 2015 Sep 1;24(17):4879-900.