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| First Name: | Harry | | Last Name: | LeVine III | | Title: | Associate Professor | | Advanced Degrees: | Ph.D. | | Affiliation: | University of Kentucky | | Department: | Molecular & Cellular Biochemistry | | Street Address 1: | Sanders-Brown Center on Aging | | Street Address 2: | 800 S.Limestone Street | | City: | Lexington | | State/Province: | KY | | Zip/Postal Code: | 40536-0230 | Country/Territory: | U.S.A. | | Phone: | 859-257-1412 | | Fax: | 859-323-2866 | | Email Address: |  |
Disclosure:
(view policy)
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View all comments by Harry LeVine III
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Alzheimer Disease, Tauopathies, Parkinson Disease, Polyglutamine Disorders (Huntington's, etc.), Prion Diseases
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A-beta PP/A-beta, Neurobiology, Molecular and Cell biology, Protein structure/chemistry
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Cornell University B.S. 1971 Biochemistry
Johns Hopkins School of Medicine Ph.D. 1975 Physiological Chemistry
Wellcome Research Laboratories, RTP, NC
postdoc 1975-1977
Positions & Employment
1977-1979 Wellcome Research Laboratories, Dept. of Molecular Biology - Research Scientist II,
RTP, NC
1979-1982 Wellcome Research Laboratories, Dept. of Molecular Biology - Research Scientist
III, RTP, NC
1982-1987 Wellcome Research Laboratories, Dept. of Molecular Biology - Research Scientist
IV, RTP, NC
1987-1991 Glaxo Research Laboratories, Dept.of Structural and Biophysical Chemistry ¡V
Research Investigator, RTP, NC
1991-1992 Parke-Davis Pharmaceutical Research, Warner- Lambert Co., Dept. of Neuroscience
Pharmacology - Senior Research Associate, Ann Arbor, MI
1992-1999 Parke-Davis Pharmaceutical Research, Dept. of Neuroscience Therapeutics -
Associate Research Fellow
1999-2000 Parke-Davis Pharmaceutical Research, Dept. of Neuroscience Therapeutics ¡V
Research Fellow
2000-2002 Pfizer Global Research, CNS Pharmacology, Ann Arbor, MI - Research Fellow
2003- Sanders-Brown Center on Aging and Dept. of Molecular and Cellular Biochemistry,
University of Kentucky, Lexington, KY - Associate Professor
Other Experience and Professional Memberships
1989-1991 Adjunct Assistant Professor, Dept. of Neurobiology, Duke University, Durham, NC
1993-2001 Adjunct Assistant Research Scientist, Dept. of Biology, University of Michigan, Ann
Arbor, MI
Spr. 2002 Lecturer II, Department of Molecular, Cellular, and Developmental Biology,
University of Michigan, Ann Arbor, MI
2/94 ¡V10/94 Acting Director, Neurodegenerative Diseases Section, Parke-Davis Pharmaceutical
Research, Dept. of Neuroscience Therapeutics
Member - NIH Special Study Section ¡V SBIR/STTR grants
Consultant- NIH/ADAMHA reviewer special study sections
Alzheimer¡¦s Disease Association reviewer
Member - Pharmaceutical Research and Manufacturer¡¦s Association Foundation¡¦s Basic Pharmacology (PhARMA) Advisory Committee
Co-organizer - Cold Spring Harbor 2000 & 2002 meetings on "Therapeutic Opportunities in Neurodegenerative Diseases"
Book Reviewer - Appraisal 1991-2002 (Northeastern Univ.) Reviews of Children's Science Education Books
Mentor - for 2 graduate students at the University of Michigan
Mentor - Women's Science for Life Program (high school student laboratory interns) 1991-2002
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LeVine, III, H. "Thioflavine T Interaction with Synthetic Alzheimer's Disease £] - Amyloid Peptides: Detection of Amyloid Aggregation in Solution", Protein Science 2: 404-410 (1993).
LeVine, III, H. "Soluble Multimeric Alzheimer £](1 40) Pre - Amyloid Complexes in Dilute Solution.", Neurobiology of Aging 16: 755-764 (1995).
LeVine, III, H. "Thioflavine T Interaction with Amyloid £]-Sheet Structures." Amyloid: The International Journal of Experimental and Clinical Investigation 2: 1-6 (1995).
LeVine, III, H. "Stopped-flow Kinetics Reveal Multiple Phases of Thioflavine T Binding to Alzheimer £](1-40)", Arch. Biochem. Biophys. 342: 306-316 (1997).
LeVine, III, H. "125I-Labeled ApoE Binds Competitively to ƒÒ(1-40) Fibrils with Pathological Chaperone Proteins", Amyloid: The International Journal of Experimental and Clinical Investigation, 7: 83-89 (2000).
Walker, L. C. and LeVine, III, H. "The cerebral proteopathies" Neurobiology of Aging 21: 559-561 (2000).
Wegiel, J., Wang, K.-C., Imaki, H., Rubenstein, R., Wronska, A., Osuchowski, M., Lipinski, WJ., Walker, LC., LeVine, III, H. ¡§The role of microglial cells and astrocytes in fibrillar plaque evolution in transgenic APPsw mice¡¨, Neurobiology of Aging 22: 49-61 (2001).
LeVine, III, H. ¡§4, 4¡¦-dianilino-1, 1¡¦-binaphthyl-5, 5¡¦-disulfonate (bis-ANS) Reports on Non-ƒÒ-Sheet Conformers of Alzheimer¡¦s Peptide ƒÒ(1-40)¡¨, Arch. Biochem. Biophys. 404: 106-115 (2002).
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1) Inability to accurately diagnose earliest stages of disease. By the time clinically probable AD is diagnosed the majority of the process is over. It is difficult to make connections of cause and effect when out of the linear regime of disease progression.
2) Lack of connection of animal models to the human condition. Extrapolation is difficult and possibly misleading.
3) Sensitive markers needed to quantify disease progression that are accurate over short time intervals- 2-3 months or less. Without these to quickly assess in early clinical phase trials whether a candidate is having the desired effect, industry will hesitate to invest properly in AD for the long term trials. |
Development of animal models that replicate more of the cellular aspects of the neurodegeneration in AD
Replace mitochondrial complement of mouse with mitochondria of normal aged and AD. This has been done at a cellular level with cells - cybrids. AD mito are different than normals.
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Alzheimer's, along with Parkinson's, Huntington's, Tauopathies, and prionoses are examples of a growing number of neurodegenerative and other diseases that are a product of cells inability to deal with toxic misfolded proteins. |
Removal, reduction, or neutralization of the toxic misfolded species slows or eliminates disease progression. |
Oxidative stress, engendered by whatever mechanisms,is a key contributor to diseases of aging, particularly those involving long-lived postmitotic cells such as neurons. At the center of this is the mitochondrion which controls ATP levels, can be a potent source of free radicals, buffers calcium fluxes directly and indirectly, and can induce apoptosis. |
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