Albert C. Ludolph

M. Flint Beal

Anthony E. Lang

Neurodegenerative diseases are major contributors to disability and disease, with Alzheimer's and Parkinson's diseases the most prevalent. This major reference reviews the rapidly advancing knowledge of pathogenesis and treatment of neurodegenerative diseases in the context of a comprehensive survey of each disease and its clinical features. The editors and contributors are among the leading experts in the field internationally. Covering basic science, diagnostic tools and therapeutic approaches, the book focuses on all aspects of neurodegenerative disease, including the normal aging process. The dementias, prion diseases, Parkinson's disease and atypical parkinsonisms, neurodegenerative ataxias, motor neuron diseases, degenerative diseases with chorea, iron and copper disorders, and mitochondrial diseases, are all methodically presented and discussed, with extensive illustrations. In each case the underlying genetics, neuropathological and clinical issues are fully reviewed, making this the most complete as well as the most authoritative reference available to clinicians and neuroscientists.

Neurobiology, Pathogenesis and Therapeutics

Neurodegenerative Diseases

Carlo Ferrarese

It can be reasonably anticipated that, over the next generations, the proportion of elderly people will remarkably increase and, with this, the number ofpersons suffering from acute (e.g. cerebral ischemia) or chronic neurodegenerative disorders. To date, approved drugs only alleviate the symptoms ofthese diseases (for instance, acetylcholinesterase inhibitors in Alzheimer disease and L-dopa and dopamine-agonists in Parkinson disease), while none seems to stop the progression of the degenerative processes underlying them. The development of effective preventive or protective therapies has been impeded by the limitations of our knowledge of the causes and the mechanisms by which neurons die in neurodegenerative disorders. Evidence accumulated in the past 20 years indicated that the major excitatory neurotransmitter glutamate may play a role as neurotoxin in several conditions. In particular, the glutamatergic system dysfunction seems to be an early event working as a common pathway in the pathogenesis ofa large number ofacute and chronic neurological disorders, in strict conjunction with other important mechanisms, such as oxidative stress and energetic failure, and probably triggered by different mechanisms in various diseases. In consideration of that, drug discovery efforts over the last decade have been focused on the search for drugs that either reduce glutamate synaptic levels or block its postsynaptic effects. Despite numerous reviews on basic mechanisms and clinical aspects ofthe excitotoxic phenomenon, so far no comprehensive book has covered the topic in all its complexity, starting from basic pharmacological mechanisms, to .animal models of diseases and finally to clinical pathogenic and therapeutic implications.

M. Flint Beal

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