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Laboratory of Research Resources (LoRRe)

Welcome to our LoRRe website !

 

About LoRRe

The Laboratory of Research Resources (LoRRe) at NCGG brings researches investigating neurodegeneration in the central nervous system. The mission of the LoRRe is to conduct multidisciplinary basic research studies that increase understanding of the causes and mechanisms leading to brain dysfunction and degeneration in neurodegenerative disorders, which are clinically characterized by dementia and motor impairment. We focus on the neurodegenerative diseases that occur more frequently with advancing age. We study brain tissues from both affected people and animal models of the diseases.

To examine the human brain tissues, we make a neuropathologic diagnosis in autopsy cases. Although social and financial issues recently play a role in the dramatic decrease in autopsy numbers, we think that the role of autopsy and diagnostic neuropathology have become more important. Then we investigate the mechanisms of neurodegeneration by utilizing the most-mortem tissues for the research. Since neurodegenerative disorders are unique to human beings, and brain tissues from other animal disease models are of limited value for the research, donating disease brain will greatly contribute to the progress towards understanding the causes and mechanism of the diseases. 

Our final goal to research on the neurodegeneration is to establish the treatment of the diseases. Our project bridges the river of numerous information on neurodegeneration from autopsy to pharmaceutical development. We investigate various drug targets and collaborate with industry partners on translational research project.
 

Ikuru Yazawa, MD, PhD

Chief, Laboratory of Research Resources (LoRRe)

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Research

Overviews of our research

1. Disease Oriented

  1. Synucleinopathies, including multiple system atrophy (MSA)
  2. Polyglutamine diseases
  3. White matter degenerative diseases 

2. Science Oriented

  1. Diagnosis and study on human post-mortem brain tissues
  2. Cellular interaction between oligodendrocytes and neurons

Overview of our research on synucleinopathies

α-Synuclein is one of the proteins fundamemental to the pathogenesis of neurodegenerative diseases. This protein forms filamentous inclusions in various neurodegenerative diseases, which are known as synucleinopathies. Synucleinopathies are pathologically classified into groups: Lewy body diseases and multiple system atrophy (MSA). Lewy body diseases, including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), exhibit the common pathological feature of neuronal cytoplasmic inclusions called Lewy bodies. α-Synuclein has been identified as the main component of Lewy bodies, and a missense mutaition in the α-synuclein gene is the genetic cause of familial Parkinsonism. Moreover, evidence implicates α-synuclein and its accumulation in PD pathogenesis. In contrast, MSA is an intractable neurodegenerative disease caused by α-synuclein accumulation in oligodendrocytes and neurons. The pathological hallmark of MSA is the presence of glial cytoplasmic inclusions (GCIs). The accumulation of α-synuclein, Levy bodies and GCIs, are found in important role in neurodegeneration observed in both PD and MSA. The α-synuclein accumulation may be the primary lesion that eventually compromises nerve cell function and viability, although the cellular mechanisms underlying each of these neurodegenerative diseases seem to be different. The scope of our activity covers all the neurodegeneration mechanisms and development of therapy to reduce the α-synuclein accumulation in PD, DLB, and MSA. We will understand the cellular mechanisms on various studies of neuropathology, molecular genetics, and animal models. Important areas for our future research include elucidation of the mechanism underlying cell-to-cell transmission of α-synuclein. We hypothesize that this transmission is caused by some molecular signals in the indirect interaction between the cells. Thus, we identify the molecular signals that are involved in this process, and determine the exact molecular structure of extracellular α-synuclein that is responsible for the pathogenic actions. Together, such information could enable us to develop effective approaches for early diagnosis and treatment of synucleinopathies. If you have some interest in our laboratory, please feel free to contact with us.

Mouse model of MSA 

(Cellular interaction between oligodendrocytes and neurons)

mouse mode of MSA

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Scientific Publications

2015

Jin C, Washimi Y, Yoshida K, Hashizume Y, and Yazawa I.

Characterization of spheroids in hereditary diffuse leukoencephalopathy with axonal spheroids.

Journal of the Neurological Sciences, 352, 74-78, 2015

2014

Suzuki Y, Jin C, Iwase T, and Yazawa I.

β-III Tubulin fragments inhibit α-synuclein accumulation in models of multiple system atrophy.

Journal of Biological Chemistry, 289, 24374–24382, 2014.
 

Suzuki Y, Jin C, and Yazawa I.

Cystatin C triggers neuronal degeneration in a model of multiple system atrophy.

The American Journal of Pathology, 184, 790-799, 2014.

 

Kinoshita M, Kondo Y, Yoshida K, Fukushima K, Hoshi K, Ishizawa K, Araki N, Yazawa I, Washimi Y, Saitoh B, Kira J, and Ikeda S.

Corpus callosum atrophy in hereditary diffuse leukoencephalopathy with neuroaxonal spheroids: an MRI-based study.

Internal Medicine, 53, 21-27, 2014.

 

Yazawa I, Suzuki Y.

α-Synuclein accumulation in Parkinson's disease and multiple system atrophy. (Polizzi M and Kanowitz HC, eds.,) α-Synuclein Functional Mechanisms, Structure and Role in Parkinson's Disease.

Nova Science Publishers, Hauppauge, NY, USA, 2014, pp.1-28.
 

2013

Suzuki Y, Jin C, and Yazawa I.

Increased aggregation of polyleucine compared with that of polyglutamine in dentatorubral-pallidoluysian atrophy protein.

Neuroscience Letters, 552, 156-161, 2013.
 

2012

Nakayama K, Suzuki Y, and Yazawa I.

Binding of neuronal α-synuclein to β-III tubulin and accumulation in a model of multiple system atrophy.

Biochemical and Biophysical Research Communications, 417, 1170-1175, 2012.

Ito H, Nakayama K, Jin C, Suzuki Y, and Yazawa I.

α-Synuclein accumulation reduces GABAergic inhibitory transmission in a model of multiple system atrophy.

Biochemical and Biophysical Research Communications, 428, 348-353, 2012.

Yazawa I.

Perspectives on therapeutic target for multiple system atrophy.

Recent Patents on Regenerative Medicine, 2, 30-36, 2012.

Yazawa I.

Tubulin: Structure, Function, and Role in Disease. (Yamauchi W and Sokic A, eds.,) Tubulin: Structure, Functions, and Roles in Disease.

Nova Science Publishers, Hauppauge, NY, USA, 2012, pp.85-100.

2011

Suzuki Y and Yazawa I.

Pathological accumulation of atrophin-1 in dentatorubralpallidoluysian atrophy.

International Journal of Clinical and Experimental Pathology, 4, 378-384, 2011.

2010

Suzuki Y, Nakayama K, Hashimoto N, and Yazawa I.

Proteolytic processing regulates pathological accumulation in dentatorubral-pallidoluysian atrophy.

FEBS Journal, 277, 4873-4887, 2010.

2009

Nakayama K, Suzuki Y, and Yazawa I.

Microtubule depolymerization suppresses α-synuclein accumulation in a mouse of multiple system atrophy.

The American Journal of Pathology, 174, 1471-1480, 2009.

Hazeki-Taylor N, Yazawa I, and Kanazawa I.

Perspectives on the therapeutic targets for Huntington's disease in view of the structural and biochemical properties of polyglutamine aggregates.

International Journal of Medical and Biological Frontiers, 15, 337-355, 2009.

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Staff

  • Chief:  Ikuru Yazawa, MD, PhD
  • Research Fellow:  Chenghua Jin, MD, PhD
  • Research Fellow:  Asuka Sasaki, PhD

LoRRe Leadership

Ikuru Yazawa, MD PhD

Research Interest and Key words

Neuropathologic diagnosis at autopsy; biochemical and genetic studies on the post-mortem tissues; neurodegeneration; animal and cellular models; α-synuclein; polyglutamine expansion; hereditary leukoencephalopathies

Description of Research and Clinical Expertise

1987  Degree of M.D. (National Examination for Medical Practitioners, Japan)

1993  Autopsy license (Ministry of Health and Welfare, Japan)

1993  Japanese Board of Clinical Neurologist

1998  Degree of Ph.D. (the University of Tokyo)

2003-2005  Visiting Scholar (University of Pennsylvania School of Medicine)

2005-present  Chief, Laboratory of Research Resources (NCGG, Japan)

Selected Previous Publications

2005
Yazawa I, Giasson BI, Sasaki R, Zhang B, Joyce S, Uryu K, Trojanowski JQ and Lee VMY. Mouse model of multiple system atrophy: α-synuclein expression in oligodendrocytes causes glial and neuronal degeneration. Neuron 45, 847-859

2000
Yazawa I. Aberrant phosphorylation of dentatorubral-pallidoluysian atrophy (DRPLA) protein complex in brain tissue. Biochem J 351, 587-591

1995
Yazawa I, Nukina N, Hashida H, Goto J, Yamada M and Kanazawa I. Abnormal gene product identified in hereditary dentatorubral-pallidoluysian atrophy (DRPLA) brain. Nat Genet 10, 99-103.

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In the News

Please help to support the LoRRe.

It is a wonderful way to support research conducted by the LoRRe. Caring individuals, through their support, make possible the scientific advances necessary for establishing a treatment for synucleinopathies and other neurodegenerative diseases.

  1. We internationally collaborate with CNDR, University of Pennsylvania School of Medicine (Drs. Virginia MY Lee and John Q Trojanowski) (2005-)
  2. We collaborate with Japanese hospitals: Laboratory of Neuropathology, Fukushimura Hospital, Aichi and Nagoya City Kosei-in Medical Welfare Center, Aichi (2011-)
  3. We collaborate with an industry partner:Ono Pharmaceutical Co. Ltd. (2014-)

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How to contact us

e-mail: yazawaik (at) ncgg.go.jp

Phone: +81-562-46-2311

Fax: +81-562-46-8319

 

Address: 7-430 Morioka-cho, Obu-shi,

Aichi-ken 474-8511, Japan

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NCGG

  • National Center for Geriatrics and Gerontology
  • National Hospital for Geriatric Medicine, NCGG
  • Center for Development of Advanced Medicine for Dementia
  • Center for Gerontology and Social Science

National Center for Geriatrics and Gerontology

7-430 Morioka-cho, Obu City, Aichi Prefecture, Japan