M.B.H. Youdim – författare

The role of the metals copper, zinc, magnesium, lead, manganese, mercury, lithium and aluminium in neuropsychiatric disease are well known and has been discussed on several occasions. Yet little attention has been paid to iron, the most abundant transitional metal in the body and the earth's crust. Iron plays a major role as a cofactor of numerous metabolic enzymes, it is important for DNA and protein synthesis, and has a crucial role in the oxygen carrying capacity of haemoglobin. Some of the most devastating diseases of systemic organs are associated with abnormal iron metabolism. Yet only very recently its role in the central nervous system has been considered. Thus nutritional iron defi­ ciency and iron overload afflict some 500-600 million people. It is also well recognized that too little or too much iron can produce profound effects on the metabolic state of the cell, and therefore the regulation of iron uptake and disposition is tightly relegated by the cell. Its transport into the cell and storage are handled by transferrin, ferritin and haemo­ siderin. Nowhere are these processes so well recognized as in the case of brain iron metabolism. Iron does not have ready access to the adult brain as it does to other tissues, since it does not cross the blood brain barrier (BBB). All the iron present in brain is deposited before the closure of BBB at an early age where it is sequestered and conserved. Therefore its turnover is extremely slow.

Monoamine oxidase plays a major role in the pathogenesis of neuropsychiatric disorders including depressive illness, Parkinson´s disease and Alzheimer´s disease. The new generation of selective monoamine oxidase inhibitors, devoid of major side effects, has found a prominent place in the treatment of these diseases. Some of these drugs may have neuroprotective activity with prospects for treating progressive neurodegenerative diseases. The volume presents a collection of research papers on monoamine oxidase and its inhibitors. The topic is treated from the point of view of chemistry, biochemistry, pharmacology, physiology, neurology and psychiatry. The book serves as a quick and comprehensive reference source for obtaining the most up to date information.

Volume 5 of the series "Advances in Research on Neurodegeneration" is concerned with themes which are currently the focus of intensive research, and in which advances in our understanding of the pathological mechanisms un­ derlying neurodegenerative diseases are expected in the near future. The first section contains five reviews devoted to the various neuroimaging technolo­ gies. The discussion is concerned with the question of whether neuroimaging techniques make it possible to follow the process of degeneration as it occurs, and which methods offer the required sensitivity and quantifiability for this purpose. However, the question needs to be examined of whether, given the physical and chemical limitations of these techniques, even under optimal conditions, anatomical resolution can be improved to the extent that neuro­ degenerative diseases can be diagnosed earlier than currently possible and a confident diagnosis made. The possibilities of using neuroimaging techniques to provide information regarding the effects of neuroprotective or neuroregen­ erative therapeutic strategies, and for correlating the results of neuropsycho­ logical research with imaging data are also discussed. The second section is concerned with the significance of endogenous or exogenous neurotoxins as triggers for neurodegenerative processes that may lead to Parkinsonism. Vulnerability factors, which include such factors as nerve ending sensitivity, the synergistic effects of drugs and the various mechanisms underlying different toxins are discussed.

Neurodegeneration is one of the most important subjects of the investigation now and in the coming 21st century. Alzheimer's disease is the leading cause of dementia in the elderly people and Parkinson's disease is one of the major neurologic disorders with the prevalence between 1 and 2/1 000 population in advanced countries. Many others are suffering from intractable neurodegener­ ative disorders such as amyotrophic lateral sclerosis, Huntington's disease, or spinocerebellar degeneration. No truly effective treatment is available for any of these neurodegenerative disorders except for Parkinson's disease; even in Parkinson's disease, still it is impossible to slow down the disease process with the currently available treatment. It is urgently needed to develop new effective technique to halt or slow down the disease process in each of those disorders. Recent advance in the molecular biological and molecular genetic technique has brought us great progress in the understanding of etiology and pathogenesis of these disorders, but still it is not known how neurons are going to die in these disorders. To explore the question, mutual cooperation and exchange of ideas between basic scientists and clinical peoples are of utmost importance.

The volume contains recent advances in research on neurodegeneration and neuroinflammation. Particular interest was focused on molecular biological aspects of the mechanism of neuronal death in neurodegenerative disorders, particularly Parkinson's disease, Alzheimer's disease, spinocerebellar degeneration and multiple sclerosis. International opinion leaders and top class researchers reviewed the progress in the above subjects. Future aspects of neuroprotection in neurodegenerative disorders and neuroinflammatory disorders were also discussed.

The 8th International Winter Conference on Neurodegeneration from Febru- ary 9 to 13, 2000 took place in Tegernsee, Bavaria, Germany. The interest shown in this symposium, which was carried by invited speakers only, was striking. 28 lectures in 5 sessions dealt with themes on basic science and therapy strategies for neurodegenerative illness. This time especially basic mechanism of cell death and resulting causal treatment possibilities were centre themes of the lectures and lively discussions. In accordance with tradi- tion 5 lectures on Multiple Sclerosis finished the convention. 60 scientists from 13 countries discussed current questions to these themes. The Symposium started with a lecture on the history of the develop- ment of modern-L-DOPA-therapy. Lectures on cell death of dopaminergic nerve cells, new valuation regarding assembly, built up and function of neuromelanin of Substantia nigra and with this, the question of the physio- logic and pathobiochemical role of dopamine and neuromelanin built the first block of themes which consequently extended to molecular and genetic aspects of cell death.Highlights of the symposium were neuroprotective and neuroregenerative future therapy strategies together with discussions on the difficulties of clinical neuroprotection. Developmental biological aspects on nerve cells, reorganisation and neurodegeneration showed a stimulating point of view of momentary and future development possibilities of new and more causal forms of therapy of neurodegenerative illness.

The 8th International Winter Conference on Neurodegeneration from Febru- ary 9 to 13, 2000 took place in Tegernsee, Bavaria, Germany. The interest shown in this symposium, which was carried by invited speakers only, was striking. 28 lectures in 5 sessions dealt with themes on basic science and therapy strategies for neurodegenerative illness. This time especially basic mechanism of cell death and resulting causal treatment possibilities were centre themes of the lectures and lively discussions. In accordance with tradi- tion 5 lectures on Multiple Sclerosis finished the convention. 60 scientists from 13 countries discussed current questions to these themes. The Symposium started with a lecture on the history of the develop- ment of modern-L-DOPA-therapy. Lectures on cell death of dopaminergic nerve cells, new valuation regarding assembly, built up and function of neuromelanin of Substantia nigra and with this, the question of the physio- logic and pathobiochemical role of dopamine and neuromelanin built the first block of themes which consequently extended to molecular and genetic aspects of cell death.Highlights of the symposium were neuroprotective and neuroregenerative future therapy strategies together with discussions on the difficulties of clinical neuroprotection. Developmental biological aspects on nerve cells, reorganisation and neurodegeneration showed a stimulating point of view of momentary and future development possibilities of new and more causal forms of therapy of neurodegenerative illness.

The 10th International Winter Conference on Neurodegeneration (lWCN) has taken place from February 14-16,2002, at the lovely "SchloB Ziethen", an old prussian manor (in Prussia, 'faute de mieux', called 'SchloB', i. e. cas- tle or residence). This place is 20 km off Tegel Airport, Berlin's main airport, and has been beautifully restored by baroness Edith von Thiingen (nee von BUlow, i. e. of historical Prussian aristocracy); it lends itself rather perfectly for the IWCN type of small interdisciplinary workshops on neurodegenera- tion which combine short lectures with plenty of discussion. In this context, we could quote Alexander von Humboldt's famous opening words for one of the first international scientific meetings held at Berlin, on September 18, 1828: "The main purpose ...does not consist in a mutual reading of manuscripts all to be printed after at least one year in specialised publications, but in the personal communication amongst those who work in similar scientific fields; the oral and thus more stimulating exchange of ideas, might they represent facts, opinions or doubts; the foundation of friendly relations which convey illumination to our sciences, serene grace to our lives and tolerance and mildness to our habits ...Berlin, Sept. 18, 1828 Alexander von Humboldt To the IWCN aficionado, it may come as a little surprise that this is the pub- lication of the 10th Winter Conference as this might mean that they must have missed number 9.

The 10th International Winter Conference on Neurodegeneration (lWCN) has taken place from February 14-16,2002, at the lovely "SchloB Ziethen", an old prussian manor (in Prussia, 'faute de mieux', called 'SchloB', i. e. cas- tle or residence). This place is 20 km off Tegel Airport, Berlin's main airport, and has been beautifully restored by baroness Edith von Thiingen (nee von BUlow, i. e. of historical Prussian aristocracy); it lends itself rather perfectly for the IWCN type of small interdisciplinary workshops on neurodegenera- tion which combine short lectures with plenty of discussion. In this context, we could quote Alexander von Humboldt's famous opening words for one of the first international scientific meetings held at Berlin, on September 18, 1828: "The main purpose ...does not consist in a mutual reading of manuscripts all to be printed after at least one year in specialised publications, but in the personal communication amongst those who work in similar scientific fields; the oral and thus more stimulating exchange of ideas, might they represent facts, opinions or doubts; the foundation of friendly relations which convey illumination to our sciences, serene grace to our lives and tolerance and mildness to our habits ...Berlin, Sept. 18, 1828 Alexander von Humboldt To the IWCN aficionado, it may come as a little surprise that this is the pub- lication of the 10th Winter Conference as this might mean that they must have missed number 9.

We organized the Seventh International Winter Conference on Neurodegeneration and Neuroinflammation in a small town of Karuizawa in Nagano Prefecture in Japan on January 20 to 22, 1999. Karuizawa is a nice summer as well as winter resort close to the place for winter Olympic game in the year of 1998. Over 40 scientists gathered together and made hot discussion. Neurodegeneration and neuroinflammation are two major and important neurologic disorders, in which satisfactory neuroprotective and neurorestorative treatment is not available yet. For this purpose, understanding of molecular mechanisms of neuronal cell death in these two disorders is imperative. Recently, pathologic processes common to these two groups of disorders have been identified such as the involvement of inflammatory changes, microglia, cytokines, and apoptosis. We intended to involve scientists working in these two major fields together to participate in hot and fruitful discussion for the understanding of neuronal death and for developing newer methods of treatment. The science is progressing so rapidly today and we are working in a very narrow specialized area. Sometimes, we are ignorant about important discoveries in other fields. This conference was a nice opportunity for scien­ tists working different areas to meet together and to exchange their experi­ ence. This volume is the proceedings of this Winter Conference.

Volume 5 of the series "Advances in Research on Neurodegeneration" is concerned with themes which are currently the focus of intensive research, and in which advances in our understanding of the pathological mechanisms un­ derlying neurodegenerative diseases are expected in the near future. The first section contains five reviews devoted to the various neuroimaging technolo­ gies. The discussion is concerned with the question of whether neuroimaging techniques make it possible to follow the process of degeneration as it occurs, and which methods offer the required sensitivity and quantifiability for this purpose. However, the question needs to be examined of whether, given the physical and chemical limitations of these techniques, even under optimal conditions, anatomical resolution can be improved to the extent that neuro­ degenerative diseases can be diagnosed earlier than currently possible and a confident diagnosis made. The possibilities of using neuroimaging techniques to provide information regarding the effects of neuroprotective or neuroregen­ erative therapeutic strategies, and for correlating the results of neuropsycho­ logical research with imaging data are also discussed. The second section is concerned with the significance of endogenous or exogenous neurotoxins as triggers for neurodegenerative processes that may lead to Parkinsonism. Vulnerability factors, which include such factors as nerve ending sensitivity, the synergistic effects of drugs and the various mechanisms underlying different toxins are discussed.

Neurodegeneration is one of the most important subjects of the investigation now and in the coming 21st century. Alzheimer''s disease is the leading cause of dementia in the elderly people and Parkinson''s disease is one of the major neurologic disorders with the prevalence between 1 and 2/1 000 population in advanced countries. Many others are suffering from intractable neurodegener­ ative disorders such as amyotrophic lateral sclerosis, Huntington''s disease, or spinocerebellar degeneration. No truly effective treatment is available for any of these neurodegenerative disorders except for Parkinson''s disease; even in Parkinson''s disease, still it is impossible to slow down the disease process with the currently available treatment. It is urgently needed to develop new effective technique to halt or slow down the disease process in each of those disorders. Recent advance in the molecular biological and molecular genetic technique has brought us great progress in the understanding of etiology and pathogenesis of these disorders, but still it is not known how neurons are going to die in these disorders. To explore the question, mutual cooperation and exchange of ideas between basic scientists and clinical peoples are of utmost importance.

The role of the metals copper, zinc, magnesium, lead, manganese, mercury, lithium and aluminium in neuropsychiatric disease are well known and has been discussed on several occasions. Yet little attention has been paid to iron, the most abundant transitional metal in the body and the earth''s crust. Iron plays a major role as a cofactor of numerous metabolic enzymes, it is important for DNA and protein synthesis, and has a crucial role in the oxygen carrying capacity of haemoglobin. Some of the most devastating diseases of systemic organs are associated with abnormal iron metabolism. Yet only very recently its role in the central nervous system has been considered. Thus nutritional iron defi­ ciency and iron overload afflict some 500-600 million people. It is also well recognized that too little or too much iron can produce profound effects on the metabolic state of the cell, and therefore the regulation of iron uptake and disposition is tightly relegated by the cell. Its transport into the cell and storage are handled by transferrin, ferritin and haemo­ siderin. Nowhere are these processes so well recognized as in the case of brain iron metabolism. Iron does not have ready access to the adult brain as it does to other tissues, since it does not cross the blood brain barrier (BBB). All the iron present in brain is deposited before the closure of BBB at an early age where it is sequestered and conserved. Therefore its turnover is extremely slow.