Journal of Neural Transmission

, Volume 116, Issue 8, pp 953–974 | Cite as

Common key-signals in learning and neurodegeneration: focus on excito-amino acids, β-amyloid peptides and α-synuclein

  • L. F. Agnati
  • G. Leo
  • S. Genedani
  • L. Piron
  • A. Rivera
  • D. Guidolin
  • K. Fuxe
Basic Neurosciences, Genetics and Immunology - Original Article


In this paper a hypothesis that some special signals (“key-signals” excito-amino acids, β-amyloid peptides and α-synuclein) are not only involved in information handling by the neuronal circuits, but also trigger out substantial structural and/or functional changes in the Central Nervous System (CNS) is introduced. This forces the neuronal circuits to move from one stable state towards a new state, but in doing so these signals became potentially dangerous. Several mechanisms are put in action to protect neurons and glial cells from these potentially harmful signals. However, in agreement with the Red Queen Theory of Ageing (Agnati et al. in Acta Physiol Scand 145:301–309, 1992), it is proposed that during ageing these neuroprotective processes become less effective while, in the meantime, a shortage of brain plasticity occurs together with an increased need of plasticity for repairing the wear and tear of the CNS. The paper presents findings supporting the concept that such key-signals in instances such as ageing may favour neurodegenerative processes in an attempt of maximizing neuronal plasticity.


Learning Neurodegeneration Excito-amino acids β-amyloid peptides α-synuclein Homocysteine 



This paper has been supported by grants from Khymeia srl (Padova); IRCCS San Camillo (Lido, Venezia); PRIN2006 (MUR, Roma), Swedish Medical Council (Sweden). We thank prof. Alexander Tarakanov (St Petersburg Institute for Informatics and Automation, Russian Academy of Sciences) for his useful comments.


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • L. F. Agnati
    • 1
    • 2
  • G. Leo
    • 1
    • 2
  • S. Genedani
    • 1
    • 2
  • L. Piron
    • 2
  • A. Rivera
    • 5
  • D. Guidolin
    • 4
  • K. Fuxe
    • 3
  1. 1.Department of BioMedical SciencesUniversity of ModenaModenaItaly
  2. 2.IRCCS San Camillo, Lido VeneziaVeneziaItaly
  3. 3.Department of NeuroscienceKarolinska InstitutetStockholmSweden
  4. 4.Department of Human Anatomy and PhysiologyUniversity of PadovaPaduaItaly
  5. 5.Department of Cell Biology, School of ScienceUniversity of MálagaMálagaSpain

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