Andrey V. Kuznetsov on a Possible Underlying Reason for Alzheimer’s Disease

Emerging Research FRonts Commentary, June 2011

Andrey V. Kuznetsov

Article: A macroscopic model of traffic jams in axons

Authors: Kuznetsov, AV;Avramenko, AA
Journal: MATH BIOSCI, 218 (2): 142-152, APR 2009
Addresses: N Carolina State Univ, Dept Mech & Aerosp Engn, Campus Box 7910, Raleigh, NC 27695 USA.
N Carolina State Univ, Dept Mech & Aerosp Engn, Raleigh, NC 27695 USA.
Natl Acad Sci Ukraine, Inst Engn Thermophys, Kiev, Ukraine.

Andrey V. Kuznetsov talks with and answers a few questions about this month's Emerging Research Front paper in the field of Mathematics.

SW: Why do you think your paper is highly cited?

I would think for at least two reasons. First, it is because the problem discussed in the paper is very important and has far-reaching practical consequences. Traffic jams in axons may be the underlying reason for Alzheimer's disease which affects a very large number of people. In order to find a cure we need first understand the mechanisms of this disease, and mathematical modeling is a very valuable tool for that. Another reason is more of a fundamental nature. Modeling of processes occurring on a microscale is a fascinating topic, especially when these processes occur inside of your brain cells.

SW: Does it describe a new discovery, methodology, or synthesis of knowledge?

I would say this is an example of what may be called a synthesis of knowledge. The project like ours is a very multi-disciplinary research, where molecular biology meets mathematics and physics of microscale dimensions. We are modeling transport of micron-sized vesicles that are propelled by molecular motors inside living cells. We would not be able to understand and describe the mechanisms involved without applying recent advances in physics, math, and molecular biology.

SW: Would you summarize the significance of your paper in layman's terms?

"Using mathematical modeling in medicine can revolutionize this field."

Many neurodegenerative diseases, such as Alzheimer's disease, Huntington and Kennedy's diseases, and the Down syndrome, are linked to swellings occurring in long arms of neurons which are called axons. Electron micrographs of cross-sections through such axonal swellings show that these swellings accumulate large amounts of intracellular organelles, which are membrane-bound vesicles containing various types of proteins and other types of cellular material.

Many scientists believe that these swellings result from traffic jams caused by the failure of intracellular machinery responsible for fast axonal transport, something similar to traffic jams in highway traffic. We developed one of the first models describing how such traffic jams in axons can develop.

SW: How did you become involved in this research, and how would you describe the particular challenges, setbacks, and successes that you've encountered along the way?

I was always fascinated by biomechanical processes. As an engineer, I am used to analyzing various processes mechanistically, and developing models of these processes based on major conservation laws, such as conservation of mass, momentum, and energy. From that perspective, our body, at the cellular or even molecular level, is a (very complex) biological machine that obeys the same laws we observe in nature. It always interested me to analyze biological systems by using the same methods that I would apply to a man-made device. I believe that we can learn a great deal about biological systems by adopting this approach.

I was very fortunate to collaborate on this research with an outstanding mathematician and engineer from the Institute of Engineering Thermophysics in Kiev, Ukraine, Dr. Andriy Avramenko. I think collaborations like this bring our countries closer together. Logistically, it also worked out great. Because of the time difference between our two counties, while I was asleep, Andriy could work on the project, send me the results by e-mail before going home, and I then could pick up where he left off. The work was virtually going 24/7.

SW: Where do you see your research leading in the future?

Well, we have pretty ambitious goals. We are thinking about modeling biochemical processes occurring inside cells in much greater detail. We would like to develop truly multi-scale biological models, which would couple molecular processes with processes occurring at a cellular level, and then the next level would be looking at the processes taking place in an organ, or even the whole organism. Such models can lead to enhancement of our understanding of biological systems and to enormous breakthroughs in medicine.

SW: Do you foresee any social or political implications for your research?

Using mathematical modeling in medicine can revolutionize this field. Instead of relying on just doctor's experience we can make diagnostics and treatment an exact science. It can also lead to better mechanistic understanding of the development of neurodegenerative diseases, enabling us to treat the cause of the disease at early stages, before any damage is done.End

Dr. Andrey V. Kuznetsov
Professor of Mechanical Engineering
Fellow of ASME
Associate Editor of the ASME Journal of Heat Transfer
North Carolina State University
Raleigh, NC, USA



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