BIOCHEMISTRY & MOLECULAR BIOLOGY
HIGHER NERVOUS SYSTEM
KAMPO MEDICINE
Dr. HIROYUKI OHYAMA.（Ph.D）
Age-related difference in synaptosomal membrane
fluidity
Biochemistry and Molecular Biology International
37,133-140,1995
Hiroyuki Ohyama, Midori Hiramatsu, Norio
Ogawa, Akitane Mori
Department of Neuroscience, Institute of
Molecular and Cellular Medicine,
Okayama University Medical School, 2-5-1
Shikatacho, Okayama 700, Japan
and *Division of Medical Science, Institute
for Life Support Technology, Yamagata Technopolis
Foundation,
Yamagata 683 Kurumanomae, Numagi, Yamagata
990, Japan
Dr. HIROYUKI OHYAMA（Ph.D） in 1995.
Age-related difference in synaptosomal membrane
fluidity
Biochemistry and Molecular Biology International
37,133-140,1995
Hiroyuki Ohyama, Midori Hiramatsu, Norio
Ogawa, Akitane Mori
Department of Neuroscience, Institute of
Molecular and Cellular Medicine,
Okayama University Medical School, 2-5-1
Shikatacho, Okayama 700, Japan
and *Division of Medical Science, Institute
for Life Support Technology, Yamagata Technopolis
Foundation,
Yamagata 683 Kurumanomae, Numagi, Yamagata
990, Japan
Dr. HIROYUKI OHYAMA（Ph.D） in 1995.
岡山大学医学博士（分子細胞医学神経情報学）
徳島大学薬学修士（生物薬品化学）
大山博行（おおやまひろゆき）
大ベストセラー
光文社 カッパブックス
痴呆症（認知症）、アルツハイマーはもう怖くない
「脳を守る漢方薬」 医学博士 大山博行
脳の老化＝アルツハイマー病に光明。 最新科学で実証された漢方薬の効果があかされる。
脳の老化とボケの関係をわかりやすく解説
認知症（痴呆症）、アルツハイマー病に対する最新情報満載
誰にでもできるボケ予防の６ヶ条を紹介
あなたも予備軍？６５歳以上の人のボケ（老人性痴呆＝認知症）発症率は７％、８５歳以上ではなんと２７％にも
BRAIN KAMPO
「 脳を守る漢方薬 」
最新科学で実証された「最新の漢方薬」とは、
漢方薬 No.1 ：老化の原因＝活性酸素を消去する
①最新の漢方薬の強力な活性酸素（フリーラジカル）消去作用、最先端機器電子スピン共鳴装置ＥＳＲを用いた実験
ヒドロキシルラジカル、スーパーオキシドラジカルを消去する
漢方薬 No.2 ：記憶の中枢＝海馬と大脳皮質を守る
②最新の漢方薬は、海馬、大脳皮質、小脳の過酸化脂質を減らす。
＊過酸化脂質：脳の老化の指標となる物質、この物質が減少していれば、脳の老化を抑制していることが示唆される。
漢方薬 No.3 ：ボケを防ぐだけでなく、長寿を約束する
③最新の漢方薬は、誘導酵素ＳＯＤ活性を高める
老化促進モデルマウス（SAM-P8＝サムピーエイト）を用いた実験
漢方薬 No.4 ：脳の血管を守って、脳細胞死を遅らせる
④最新の漢方薬の脳循環改善作用、脳代謝改善作用、遅発性神経細胞壊死DND改善作用
DND=Delayed Neuronal Death とは、
漢方薬 No.5 ：脳内神経伝達物質（ニューロトランスミッター）の合成を促す
⑤最新の漢方薬のＣＡＴ（キャット）活性増強作用
ＣＡＴ（コリン・アセチル・トランスフェラーゼ）とは、
漢方薬 No.6 ：脳内の異常な興奮を鎮め、てんかん発作を抑える
⑥最新の漢方薬の異常脳波（てんかん発作波）正常化作用
キンドリングキャットを用いた実験
漢方薬 No.7 ：神経突起を伸ばし、脳細胞の失われたネットワーク（記憶の痕跡）を再生する
⑦最新の漢方薬の神経突起伸展作用、ラット初代培養神経細胞を用いた実験、
成長円錐 ＧＣ（Growth Cone）とは、
神経細胞毒（サイトカラシンＢ）を用いた実験
脳神経細胞のルーピング現象とは、
漢方薬 No.8 ：アルツハイマー病に特徴的な「空間認知障害」を防ぐ
⑧最新の漢方薬の８方向放射状迷路装置を用いた実験
空間認知（Spatial Cognition）とは、
漢方薬 No.9： 漢方薬①～⑧の作用を併せ持つ
「自分で煎じて飲むことができ、副作用がない」
Produced by
Dr. HIROYUKI OHYAMA.（Ph.D）
Depertment of Neurochemistry, Institute for
Neurobiology,
Okayama University Medical School
（ Director : Professor Akitane Mori ）
March 28, 1995
Reference
1) Effect of Kampo Medicine Preparations
Using the Pathological Model of Dementia
Michihiro Fujiwara
Brain Research Conference for Japanese Kampo
Medicine
pp.67-81,1990
2) Mixed Japanese Herbs and Age-Related Neuronal
Functions
Midori Hiramatsu and Makiko Komatsu
Antioxidant Food Supplements in Human Health,edited
by Lester Packer,
Midori Hiramatsu,Toshikazu Yoshikawa,
pp.412-428,1999
3) Effects of Japanese herbal medicine(TJ-960),
on neuronal membrane fluidity of mice
Hiroyuki Ohyama,Midori Hiramatsu,Rei Edamatsu,Akitane
Mori.
Magnetic Resonance in Medicine
6,279-281,1995
4) Antioxidant effect of TJ-960, a Japanese
herbal medicine, against free radical-induced
neuronal cell damage
Akitane Mori, Hajime Hamada, Hiroyuki Ohyama,
Midori Hiramatsu, Seiichi Shinohara
International Symposium on Natural Antioxidants:
Molecular Mechanisms and Health Effects(ISNA),
pp.45-53.1996
5) Effect of TJ-960 on generalized seizure
in amygdaloid kindled cats
Susumu Iizuka, Atsushi Ishige, Kyoji Sekiguchi,
Akira Sugimoto, Kouichi Itoh, Masaki Aburada,
Eikichi Hosoya, Eiichi Sugaya
Recent Advances in the Pharmacology of Kampo
Medicines
pp.62-68,1988
6) Normalizing effect of SK commercial formula
on cytochalasin-B
distorted neurites using primary cultured
neurons of rat cerebeal cortex
Aiko Sugaya, Mitsutoshi Yuzurihara, Tadashi
Tsuda, Eiichi Sugaya
J. Ethnopharmacol., 21: 193-199,1987.
7) Effect of Kampo Medicine Preparations
Using the Pathological Model of Dementia
Michihiro Fujiwara
Brain Research Conference for Japanese Kampo
Medicine
pp.67-81,1990
Copyright Kobunsha
大ベストセラー
光文社 カッパブックス
痴呆症（認知症）、アルツハイマーはもう怖くない
「脳を守る漢方薬」 医学博士 大山博行
定価（本体８１９円＋税）
KAPPA BOOKS
ISBN4-334-00650-7
C0247 ￥819
1991
" THE KAMPO "
" KAMPO 漢方 "
How the Japanese Updated Traditional Herbal
Medicine
Akira Tsumura, the Author
About the Author :
Akira Tsumura has unique qualifications to
brief us in the Western world
on the history and benefits of Japanese herbal
medicine.
The pharmaceutical firm he heads has a long
family tradition.
Tsumura, Inc. was founded by his grandfather,
Jusha Tsumura,
and has diversified to become the leading
supplier of herbal medicinals.
Sub-sidiaries in the United States are well-known
distributors
of health and beauty care products.
At Tsumura, Inc. scientists using the latest
technology
are testing the properties of various ancient
Kampo medication.
In the Tokyo suburb of Tsuchiura, the firm
has constructed a modern,
high-tech factory using robots for difficult
research procedures.
The auther also has a warm appreciation of
the needs
and attitudes of the American people.
His interest in Western culture has remained
strong since he pursued a degree
in business management at the University
of Michigan in Ann Arbor.
He has formed his own Dixieland jazz group
in Japan, the Storyville Dandies !!!
His collection of vintage banjoes is the
best in the world. 
" THE KAMPO "
1991
資料提供
大山漢方堂薬局
KAMPO MEDICINE
Tradition Guiding Innovation
Report of the 100th Anniversary International
Kampo Symposium '93 Tokyo, Japan
9-10 April 1993
Medicines of Plant Origin
Patient Benefit and
Japanese Kampo Therapy 1991
Program and Book of Abstracts
Report of an International Scientific
Workshop held in Bergen, Norway
31 May 1991
Recent Advances in the Pharmacology of
KAMPO MEDICINES
（JAPANESE HERBAL MEDICINES）
Proceedings of the Satellite Meeting on Kampo（Japanese
Herbal） Medicines
of the 10th International Congress of Pharmacology,
Auckland, New Zealand, August 19-21, 1987
Basic and Clinical Studies of TJ-23 on Alzheimer's
Dementia
Brain Research Conference for Japanese Kampo
Medicine
1990
資料提供
大山漢方堂薬局
The First International Conference on Senescence:
The SAM Model
March 17-18,1994 Kyoto, Japon
PROCEEDINGS OF THE FIRST SAM KYOTO SYMPOSIUM
THE COUNCIL FOR SAM RESEARCH
Dept.of pathology chest disease res.inst.,
Kyoto university,Japan.1988
This Issue Devoted to
Proceedings of the 18th Collegium Internationale
Neuro-Psychopharmacologicum Congress
Clinical Neuropharmacology
Collegium Internationale Neuro-Psychopharmacologium
18th C.I.N.P. CONGRESS
ACROPOLIS Convention Center,
Nice, France
June 28 - July 2, 1992
資料提供
大山漢方堂薬局
Medicines of Plant Origin in Modern Therapy
from the 4th World Conference on Clinical
Pharmacology, Prague 1989
A SYMPOSIUM REPORT
Published by Oxford Clinical Communications,
1989
The English Guide to Medicinal Plants
and Kampo Formulae
1993
HERBAL MEDICINE : KAMPO,
Past and Present
1985
資料提供
大山漢方堂薬局
EUROPEAN JOURNAL OF PHARMACOLOGY
11th International Congress of Pharmacology
Amsterdam, The Netherlands
1-6 July, 1990
Free Radicals in Brain Physiology and Disorders
An International Conference
Held in Celebration of the Retirement of
Professor Akitane Mori
August 4 and 5, 1995
International Convention Center PAMIR,
Tokyo,Japan
資料提供
大山漢方堂薬局
「脳を守る漢方薬」
脳の老化とボケの関係をわかりやすく解説
認知症（痴呆症）、アルツハイマー病に対する最新情報満載
誰にでもできるボケ予防の６ヶ条を紹介
著者
医学博士 大山博行
Dr.HIROYUKI OHYAMA（Ph.D）
研究業績
漢方を現代病に活かす！大山漢方堂薬局
鍼灸を現代病に活かす！医学博士 大山博行
医学博士 大山博行
Dr.HIROYUKI OHYAMA（Ph.D）
大山宗伯東洋医学記念館
' sohhaku OHYAMA ' memorial
Institute of Natural Health Science
大山宗伯東洋医学記念館
Image of Ohyama Kampo
" KEIRAKU "
Kampo brewer
Medicine chests
Image of Ohyama Kampo
Prescription drawer chest found in pharmacies
during the edo period
Kampo brewer made of metal
Used to grind crude drugs made of metal
Medicine chests
Image of Ohyama Kampo
Image of Ohyama Kampo
sohhaku OHYAMA memorial
Oriental Medicine
（Kampo medicines, Acupuncture & Moxibustion）
Museum
「1006」
「NAMBU]
「GOTOKU」
「YAKUKAN, YAKUTUBO & GOTOKU」
「Haribako」
Acupuncture & Moxibustion Box
「Kyubako」
「Medicine Cases」
「Medicine Cabinets」
「SAMURAI」
the edo period
「ATSUHIME」
「YAKUMI-TANSU」
JAPANESE HERBAL MEDICINES
KAMPO MEDICINES
JAPANESE HERBAL MEDICINES
KAMPO MEDICINES
Image of Ohyama Kampo
Reference
BIOCHEMISTRY & MOLECULAR BIOLOGY
A.S.B.M.B
DR.HIROYUKI OHYAMA（Ph.D）
1)
Age-related difference in synaptosomal membrane
fluidity
Hiroyuki Ohyama, Midori Hiramatsu, Norio
Ogawa, Akitane Mori
Biochemistry and Molecular Biology International
37,133-140,1995
Department of Neuroscience, Institute of
Molecular and Cellular Medicine, Okayama
University Medical
School, 2-5-1 Shikatacho, Okayama 700, Japan
and *Division of Medical Science, Institute
for Life
Support Technology, Yamagata Technopolis
Foundation, Yamagata 683 Kurumanomae, Numagi,
Yamagata 990, Japan
2)
Effect of Japanese herbal medicine(TJ-960)
on neuronal membrane fluidity of mice
Hiroyuki Ohyama, Midori Hiramatsu, Rei Edamatsu,
Akitane Mori
Magnetic Resonance in Medicine 6, 279-281,
1995
3)
Effect of Japanese herbal medicine(TJ-960),
on aging
Midori Hiramatsu, Rei Edamatsu, Hiroyuki
Ohyama, Akitane Mori
Lipid-Soluble Antioxidants:Biochemistry and
Clinical Applications.
pp.535-552,Birkhauser Verlag,Basel,1992
4)
Combined treatment of Japanese herbal medicine(TJ-960)with
low dose of dipropylacetate increased the
latent time for
pentylenetetrazol induced convulsion and
decreased brain lipid peroxidation in mice.
Hiramatsu,M., Liu J, Edamatsu,R., Kadowaki,D.,
Hamada,H., Ohyama,H., Watanabe,S., Mori,A.
Neuroscience 18, 71-76,1992
5)
Estimation of nitric oxide and nitric oxide
synthase activity in SAMP8 mouse brain
Habu,H., Yokoi,I., Kabuto,H., Ohyama,H.,
Mori,A., Teraoka,H., Komaru,N.
in: The SAM Model of Senescence (T.Takeda,
ed.) pp.343-346,Elsevier Science B.V., Amsterdam,
1994
6)
Age-related changes in nitric oxide content
and nitric oxide synthase activity
in senescence-accelerated mouse (SAM P8)
brain
Yokoi,I., Inada,K., Habu,H., Kabuto,H., Mori,A.,
Ohyama,H., Iwaya,K., Koyama,S., Nishijima,Y.,
Nishijima,K.
in: Oxidative Stress and Aging (R.G.Cutler,
L.Packer, J.Bertram, A.Mori, eds.)
pp387-391, Birkhauser Verlag, Basel, 1995
7)
UNESCO / Costam Workshop on Lipid-soluble
Antioxidants in Biochemistry of Nutrition
and Environmental Health
1991.9.21 (Malaysia)
Effect of Japanese herbal medicine(TJ-960),
on aging
Midori Hiramatsu, Rei Edamatsu, Hiroyuki
Ohyama, Akitane Mori
8)
Society for Free Radical Research 1991.9027
(Paris)
Japanese herbal medicine(TJ-960) affected
free radicals, SOD activity,
lipid peroxidation and neurotransmitter in
aged rat brain
Midori Hiramatsu, Rei Edamatsu, Hiroyuki
Ohyama, Akitane Mori
9)
5th International Congress on Oxygen Radicals
1991.11.18 (Kyoto)
Decreased membrane fluidity in rat synaptosomes
induced by active oxygen species,
guanidino compounds and convulsants
Midori Hiramatsu, Rei Edamatsu, Hajime Hamada,
Hiroyuki Ohyama, Akitane Mori
10)
5th International Congress on Oxygen Radicals
1991.11.20 (Kyoto)
Antioxidant effects of the extracts of gastrodia
fleta bl. and uncaria rhynchophylla (MJQ)
jacks
Jiankang Liu, Hajime Hamada, Hiroyuki Ohyama,
Akitane Mori.
11)
The First International Conference on Senescence:
The SAM Model 1994.3.17 (Kyoto)
Estimation of nitric oxide and nitric oxide
synthase activity in SAMP8 mouse brain
Habu,H., Yokoi,I., Kabuto,H., Ohyama,H.,
Mori,A., Teraoka,H., Komaru,N.
12)
The First International Conference on Oxidative
Stress and Aging 1994.3.25 (Hawaii)
Age-associated changes in nitric oxide (NO)
content and nitric oxide synthase (NOS) activity
in senescence accelerated mouse (SAM P8)
brain
Yokoi,I., Inada,K., Habu,H., Kabuto,H., Mori,A.,
Ohyama,H., Iwaya,K., Koyama,S., Nishijima,Y.,
Nishijima,K.
13)
International Conference on Bioradicals Detected
by ESR Spectroscopy 1994.6.13 (Yamagata)
Effect of Japanese herbal medicine(TJ-960)
on neuronal membrane fluidity of mice
Hiroyuki Ohyama, Midori Hiramatsu, Rei Edamatsu,
Akitane Mori
14)
International Symposium on Natural Antioxidants:
Molecular Mechanisms and Health Effects (ISNA)
1995.6.21 (Beijin)
Antioxidant defenses of Japanese herbal medicine(TJ-960)
, against free radical induced neural cell
damages
Akitane Mori, Hajime Hamada, Hiroyuki Ohyama,
Midori Hiramatsu, Seiichi Shinohara
Reference
1)
Mixed Japanese Herbs and Age-Related Neuronal
Functions
Midori Hiramatsu and Makiko Komatsu
Antioxidant Food Supplements in Human Health,edited
by Lester Packer,
Midori Hiramatsu,Toshikazu Yoshikawa,pp.412-428,1999
2)
Effects of Japanese herbal medicine(TJ-960),
on neuronal membrane fluidity of mice
Hiroyuki Ohyama,Midori Hiramatsu,Rei Edamatsu,Akitane
Mori.
Magnetic Resonance in Medicine 6,279-281,1995
3)
Antioxidant effect of TJ-960, a Japanese
herbal medicine, against free radical-induced
neuronal cell damage
Akitane Mori, Hajime Hamada, Hiroyuki Ohyama,
Midori Hiramatsu, Seiichi Shinohara
International Symposium on Natural Antioxidants:
Molecular Mechanisms and Health Effects(ISNA),pp.45-53.1996
4)
Effect of TJ-960 on generalized seizure in
amygdaloid kindled cats
Susumu Iizuka, Atsushi Ishige, Kyoji Sekiguchi,
Akira Sugimoto, Kouichi Itoh, Masaki Aburada,
Eikichi Hosoya, Eiichi Sugaya
Recent Advances in the Pharmacology of Kampo
Medicines pp.62-68,1988
5)
Normalizing effect of SK commercial formula
on cytochalasin-B distorted neurites using
primary cultured neurons of rat cerebeal
cortex
Aiko Sugaya, Mitsutoshi Yuzurihara, Tadashi
Tsuda, Eiichi Sugaya
J. Ethnopharmacol., 21: 193-199,1987.
6)
Effect of Kampo Medicine Preparations Using
the Pathological Model of Dementia
Michihiro Fujiwara
Brain Research Conference for Japanese Kampo
Medicine pp.67-81,1990
7)
Estimation of nitric oxide and nitric oxide
synthase activity in SAMP8 mouse brain
Habu,H.,Yokoi,I.,Kabuto,H.,Ohyama,H.,Mori,A.,Teraoka,H.,Komaru,N.
The SAM Model of Senescence(T.Takeda,ed.)
pp.343-346,
Elsevier Science B.V.,Amsterdam,1994
8)
Mixed Natural Antioxidants
Hiramatsu,M.
Food and Free Radicals,edited by Hiramatsu
et al.
Plenum Press,New York,pp.113-117,1997
DR.HIROYUKI OHYAMA（Ph.D）
BIOCHEMISTRY & MOLECULAR BIOLOGY
HIGHER NERVOUS SYSTEM
KAMPO MEDICINE
Dr. HIROYUKI OHYAMA.（Ph.D）
1999
Reference
A.S.B.M.B
BIOCHEMISTRY & MOLECULAR BIOLOGY
References １
(1) Whitehouse P.J., Price D.L. and Struble
R.G. Alzheimer's disease and senile dimentia:
loss of neurons in the basal forebrain. Science
215, 1237-1239, 1982.
(2) Price D.L., Whitehouse P.J. and Struble
R.G. Alzheimer's diseases. Ann. Rev. Med.
36, 349-356, 1985.
(3) Appleyard M.E., Smith A.D., Wilcock G.K
and Esiri M.M. Decreased CSF acetylcholinesterase
activity in Alzheimer's disease. Lancet 20,
452, 1983
(4) Lovell M.A., Ehmann W.D., Butler S.M.
and Markesbery W.R. Elevated thiobarbituric
acid reactive substances and antioxident
enzyme activity
in the brain in Alzheimer's disease. Neurology
45, 1594-1601, 1995.
(5)Mutisya E.M., Bowling A.B. and Beal M.F.
Cortical cytochrome oxidase activity is reduced
in Alzheimer's disease. J. Neurochem. 63,
2179-2184, 1994.
(6) Hensley K., Carney J.M., Mattson M.P.,
Aksenova M., Harris M., Wu J.F. and Floud
R.A. A model for α-amyloid aggregation and
neurotoxicity based
on free radical generation by the peptide:
Relevance to Alzheimer disease. Proc. Natl.
Acad. Sci. USA 91, 3270-3274, 1994.
(7) Kasai H. and Nishimura S. Hydroxylation
of deoxyguanosine at the C-8 position by
ascorbic acid and other reducing agents.
Nucleic Acids Res. 12, 2137-2145, 1984.
(8) Shibutani S., Takeshita M. and Grollman
A.P. Insertion of specific nases during DNA
synthesis past the oxidation damage base
8-oxodG. Nature 349, 431-434, 1991.
(9) Cheng K.C., Cahill D.S., Kasai H., Nishimura
S. and Loeb L.A. 8-Hydroxyguanine, an abundant
form of oxidative DNA damage,
causes G→T and A→C substitutions. J. Biol.
Chem. 267, 166-172, 1992.
(10) Prasad G.S., Lovell M.A. and Markesbery
W.R. Increased nuclear DNA oxidation in the
brain in Alzheimer's diseases. J. Neurochem.
71, 2034-2040, 1998.
(11) Sohal R.S., Agarwal S. and Sohal B.H.
Oxidative stress and aging in the Mongolian
gerbil (Meriones unquiculatus). Mech. Ageing
and Dev. 81, 15-25, 1995.
(12) Asuncion J.G., Millan A., Pla R., Bruseghini
L, Esteras A., Pallardo F.V., Sastre J. and
Vina J. Mitochondrial glutathione oxidation
correlates
with age-associated oxidative damage to mitochondrial
DNA. FASEB J. 10, 333-338, 1996.
(13) Sastre J., Millan A., Asuncion J.G.,
Pla R., Juan G., Pallardo F., O'Conner E.,
Martin J.A., Droy-Refaix M.T. and Vina J.
A Ginkgo biloba extract (EGb 761)
prevents mitochondrial aging by protecting
against oxidative stress. Free Rad. Biol.
Med. 24, 298-304, 1998.
(14) Mecocci P., Fano G., Fulle S., MacGarvey
U., Shinobu L., Polidori M.C., Cherubini
A., Vecchiet J., Senin U. and Beal M.F. Age-dependent
increases
in oxidative damage to DNA, lipids, and proteins
in human skeletal muscle. Free Rad. Biol.
Med. 26, 303-308, 1999.
(15) Ciani E., Groneng L., Voltattorni M.,
et al. Inhibition of free radical production
or free radical scavenging protects from
the excitotoxic cell death mediated
by glutamate in cultures of cerebellar granule
neurons., Brain Res. 728, 1-6, 1996.
(16) Dawson V.L. and Dawson T.M. Free radicals
and neuronal cell death. Cell Death and Differentiation
3, 71-78, 1996.
(17) Pillot T., Drouet B., Queille S., Labeur
C., Vandekerckhove J., Rosseneu M., Pincon-Raymond
M. and Chambaz J.
The nonfibrillar amyloid _-peptide induces
apoptotic neuronal cell death: Involvement
of its c-terminal fusogenic domain. J. Neurochem.
73, 1626-1634, 1999.
(18) Herbison A.E., Augood S.J. and Slmonian
S.X. Regulation of GABA transport activity
and mRNA expression
by estrogen in rat preoptic ares. J. Neurosci.
15, 8302-8309, 1995.
References 2
1. Chartier-Harlin,M.C. et al. Early-onset
Alzheimer's disease caused bymutations at
codon precursor protein gene. Nature 353,
844-846 (1991).
2. Sherrington,R.et al. Cloning of a gene
bearing missense mutations inearly-onset
familial Alzheimer's disease. Nature 375,
754-760 (1995).
3. Rogaev,E.I. et al. Familial Alzheimer's
disease in kindreds withmissense mutations
in a gene on chromosome 1 related to the
Alzheimer'sdisease type 3 gene. Nature 376,
775-778 (1995).
4. Borchelt,D.R. et al. Familial Alzheimer's
disease-linked presenilin 1variants elevate
Abeta1-42/1-40 ratio in vitro and in vivo.
Neuron 17,1005-1013 (1996).
5. Duff,K. et al. Increased amyloid beta42
(43) in brains of miceexpressing mutant presenilin
1. Nature 383, 710-713 (1996).
6. Nakano,Y.et al. Accumulation of murine
amyloid beta42 with a gene-dosagedependent
manner in PS1 'knock-in' mice. Eur.J.Neurosci.
11, 2577-2581(1999).
7. Iwatsubo,T. et al. Visualization of A?42
(43) and A?40 in senileplaques with end-specific
A?monoclonals: evidence that an initiallydeposited
species is A?42 (43). Neuron 13, 45-53 (1994).
8. Scheuner,D. et al. Secreted amyloid beta-protein
similar to that in thesenile plaques of Alzheimer's
disease is increased in vivo by thepresenilin
a and 2
and APP mutations linked to familial Alzheimer'sdisease.
Nature Med. 2, 864-870 (1996).
9. Wong,P.C. et al. Presenilin 1 is required
for Notch and Dll1 expressionin the paraxial
mesoderm. Nature 387, 288-292 (1997).
10. Davis,J.A. et al. An Alzheimer's disease-linked
PS1 variant rescues thedevelopmental abnormalities
of PS1-deficient embryos. Neuron 20, 603-609(1998).
11. De Strooper,B. et al. Deficiency of presenilin-1
inhibits the normalcleavage of amyloid precursor
protein. Nature 391, 387-390 (1998).
12. Wolfe,M.S. et al. Two transmembrane aspartates
in presenilin-1required for presenilin endoproteolysis
and gamma-secretase activity.Nature 398,
513-517 (1999).
13. Guo,Q.et al. Alzheimer's presenilin mutation
sensitizes neural cells toapoptosis induced
by trophic factor withdrawal
and amyloid?-peptide:involvement of calcium
and oxyradicals. J.Neurosci. 17, 4212-4222
(1997).
14. Guo,Q.et al. Increased vulnerability
of hippocampal neurons toexcitotoxic necrosis
in presenilin-1 mutant knock-in mice. Nature
Med. 5,101-106 (1999).
15. Sidrauski,C.et al. The unfolded protein
response: an intracellularsignalling pathway
with many surprising features. Trends in
Cell Biol. 8,245-249 (1998).
16. Tirasophon,W. et al. A stress response
pathway from the endoplasmicreticulum to
the nucleus requires
a novel bifunctional proteinkinase/endoribonuclease
(Ire1p) in mammalian cells. Genes Dev. 12,1812-1824(1998).
17. Wang,X-Z.et al. Cloning of mammalian
Ire1 reveals diversity in the ERstress responses.
EMBO J. 17, 5708-5717 (1998).
18. Katayama, T. et al. Presenilin-1 mutations
downregulate the signalling pathway of unfolded
protein response. Nature Cell Biol. in press
(1999).
19. Iwatsubo, T. et al. Purification and
characterization of Lewy bodiesfrom the brains
of patients with diffuse Lewy body disease.
Am.J.Pathol.148, 1517-1529 (1996).
20. DiFiglia,M. et al. Aggregation of huntingtin
in neuronal intranuclearinclusions and dystrophic
neurites in brain. Science 277, 1990-1993(1997).
References 3
1) Raff, M. C., Barres, B. A., Burne, J.
F., Coles, H. S., Ishizaki, Y., and Jacobson,
M. D. (1993)
Programmed cell death and the control of
cell survival: lessons from the nervous system.
Science, 262:695-700.
2) Purves, D.(1988) "Body and Brain"
Harverd University Press.
3) Levi-Montalcini, R. And Angeletti, P.
(1968)
Nerve growth factor, Pysiol. Rev., 48:534-569.
4) Cohen, S. And Levi-Montalcini, R. (1956)
A nerve growth-stimulating factor isolated
from snake venom. Proc. Natl. Acad Sci. USA,
42:571-574.
5) Johnson, E. M., Gorin, P. D., Brandeis,
L. D. And Pearson, J. (1980)
Science, 210:916-918.
6) Smeyne, R. J., Klein, R., Schnapp, A.,
Long, L. K., Bryant, S., Lewin, S. A. and
Barbacid, M. (1994)
Severe sensory and sympathetic neuropathies
in mice carrying a disrupted Trk/NGF. Nature,
368:246-248.
7) Davies, A. M., Enokido, Y. and Wyatt,
S.(1999)
Paradigms of neurotrophic factor action in
regulating neuronal survival in the developing
nervous system. Taniguchi Symposium, in press.
8) Davies, A. M., Bandtlow, C., Heumann,
R., Korsching, S., Rohrer, H. And Thoenen,
H. (1988)
Timing and site of nerve growth factor synthesis
in developing skin in relation to innervation
and expression of the receptor. Nature, 326:353-358.
9) Wyatt, S. And Davies, A. M.(1993)
Regulation of expression of mRNAs encoding
the nerve growth factor receptors p75 and
trkA in developing sensory neurons. Development,
119:635-648.
10) Buchman, V. L., and Davies, A. M.(1993)
Different neurotrophins are expressedand
act in a developmental sequence to promote
the survival of embryonic sensory neurons.
Development, 118: 989-1001.
11) Davies, A. M. (1997)
Neurotrophin switching: where does it stand?
Curr. Opin. Neurobiol.,7:110-118.
12) Verdi, J. M. And Anderson, D. J. (1994)
Neurotrophins regulate sequential changes
in neurotrophin receptor expression by sympathetic
neuroblasts.Neuron, 13:1359-1372.
13) Wang, H. And Tessier-Lavigne, M.(1999)
En passant neurotrophic action of and intermediate
axonal target in the developing mammalian
CNS. Nature, 401;765-769.
14) Davies , A. M. and Wright, E. M. (1995)
Neurotrophin autocrine loops. Curr. Biol.,
5:723-726.
15) ElShamy, W. M., Fridvall, L. K. and Ernfors,
P.(1998)
Growth arrest failure, G1 restriction point
override, and S phase death of sensory precursor
cells in the absence of neurotrophin-3.Neuron,
21:1003-15
16) Enokido, Y., Wyatt, S. and Davies, A.
M. (1999)
Developmental changes in the response of
trigeminal neurons to neurotrophins: influence
of birthdate and the ganglion environment.
Development, 126:4365-4373.
17) Ma, Q., Fode, C., Guillemot, F. and Anderson,
D. J.(1999)
NEUROGENIN1 and NEUROGENIN2 control two distinct
waves of neurogenesis in developing dorsal
root ganglia. Genes & Dev., 13:1717-1728.
18) Ma, Q., Chen, Z., del Barco Barrantes,
I., de la Pompa, J. L. and Anderson, D. J.
(1998)
Neurogenin1 is essential for the determination
of neuronal precursors for proximal cranial
sensory ganglia. Neuron, 20:469-82
19) Fode, C., Gradwohl, G., Morin, X., Dierich,
A., LeMeur, M., Goridis, C. and Guillemot,
F. (1998)
The bHLH protein NEUROGENIN 2 is a determination
factor for epibranchial placode-derived sensory
neurons. Neuron, 20:483-94
20) O'Connor, R. and Tessier-Lavigne, M.(1999)
Identification of maxillary factor, a maxillary
process-derived chemoattractant for developing
trigeminal sensory axons. Neuron, 24:165-178.
21) Lumsden, A. G., and Davies, A. M. (1983)
Earliest sinsory nerve fibers are guided
to peripheral targets by attractants other
than nerve growth factor. Nature,306:786-788.
22) Tessier-Lavigne, M., and Placzek, M.
(1991)
Target attraction: are developing axons guided
by chemotropism? Trends Neurosci., 14:303-310.
23) Blasschke, A. J., Staley, K. and Chun,
J.(1996)
Widespread programmed cell death in proliferative
and postmitotic regions of the fetal cerebral
cortex. Development, 122:1165-1174.
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