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Excitotoxicity in Neurological Diseases

New Therapeutic Challenge

  • Carlo Ferrarese
  • M. Flint Beal

Table of contents

  1. Front Matter
    Pages i-xii
  2. Introduction and Historical Notes

    1. M. Flint Beal
      Pages 1-9
  3. Basic Mechanisms

    1. Front Matter
      Pages 13-13
    2. Daniela Rossi, Paola Bezzi, Maria Domercq, Liliana Brambilla, Jacopo Meldolesi, Andrea Volterra
      Pages 13-26
    3. Danbolt N C, Holmseth S, Skår A, Lehre K P, Furness D N
      Pages 27-49
    4. Fabrizio Gardoni, Flaminio Cattabeni, Monica Di Luca
      Pages 51-63
    5. Maria Passafaro, Carlo Sala
      Pages 65-77
    6. Valeria Bruno, Giuseppe Battaglia, Ferdinando Nicoletti
      Pages 79-102
  4. Acute and Chronic Neurological Disorders

    1. Front Matter
      Pages 135-135
    2. Domenico E. Pellegrini-Giampietro, Elena Meli, Flavio Moroni
      Pages 171-188
    3. Niklas Marklund, John F. Stover, Tracy K. McIntosh
      Pages 189-215
    4. Antonio Pisani, Paolo Calabresi
      Pages 229-242
    5. M. Flint Beal
      Pages 243-249
    6. Judyth Sassoon, Filmore Banks, David R. Brown
      Pages 263-283
    7. David Pitt, Cedric S. Raine
      Pages 285-303
    8. Marcus Kaul, Stuart A. Lipton
      Pages 305-315
    9. Simone Beretta, Angelo Aliprandi, Carlo Ferrarese
      Pages 317-337
    10. Laura Brighina, Angelo Aliprandi, Simone Beretta, Carlo Ferrarese
      Pages 339-354
  5. Back Matter
    Pages 355-362

About this book

Introduction

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.

Keywords

Alzheimer Parkinson alzheimer's disease brain brain injury cerebral ischemia dementia glutamate receptor neurons oxidative stress receptor trauma traumatic brain injury

Editors and affiliations

  • Carlo Ferrarese
    • 1
  • M. Flint Beal
    • 2
  1. 1.Department of Neurology and NeuroscienceUniversity of Milano-BicoccaMonza (Milano)Italy
  2. 2.Department of Neurology and NeuroscienceWeill Medical College of Cornell UniversityNew YorkUSA

Bibliographic information