Proteopathic Seeds and Neurodegenerative Diseases

1. Front Matter

   Pages i-xi

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2. Widening Spectrum of Prions Causing Neurodegenerative Diseases

   • Stanley B. Prusiner

   Pages 1-17

3. β-Amyloid Fibril Structures, In Vitro and In Vivo

   • Robert Tycko

   Pages 19-31

4. Structure-Activity Relationship of Amyloids

   • Jason Greenwald, Roland Riek

   Pages 33-46

5. Seeding and Cross-seeding in Amyloid Diseases

   • Per Westermark, Gunilla T. Westermark

   Pages 47-60

6. The Prion-Like Aspect of Alzheimer Pathology

   • Sarah K. Fritschi, Bahareh Eftekharzadeh, Giusi Manfredi, Tsuyoshi Hamaguchi, Götz Heilbronner, Amudha Nagarathinam et al.

   Pages 61-69

7. Amyloid-β Transmissibility

   • C. Duran-Aniotz, R. Morales, I. Moreno-Gonzalez, C. Soto

   Pages 71-86

8. Prion-Like Properties of Assembled Tau Protein

   • Florence Clavaguera, Markus Tolnay, Michel Goedert

   Pages 87-95

9. Accumulating Evidence Suggests that Parkinson’s Disease Is a Prion-Like Disorder

   • Nolwen L. Rey, Elodie Angot, Christopher Dunning, Jennifer A. Steiner, Patrik Brundin

   Pages 97-113

10. Propagation and Replication of Misfolded SOD1: Implications for Amyotrophic Lateral Sclerosis

    • Anne Bertolotti

    Pages 115-122

11. Development of Drugs That Target Proteopathic Seeds Will Require Measurement of Drug Mechanism in Human Brain

    • Peter T. Lansbury Jr

    Pages 123-130

12. The Role of Functional Prions in the Persistence of Memory Storage

    • Eric R. Kandel, Irina Derkatch, Elias Pavlopoulos

    Pages 131-152

13. Back Matter

    Pages 153-155

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The misfolding and aggregation of specific proteins is an early and obligatory event in many of the age-related neurodegenerative diseases of humans. The initial cause of this pathogenic cascade and the means whereby disease spreads through the nervous system, remain uncertain. A recent surge of research, first instigated by pathologic similarities between prion disease and Alzheimer’s disease, increasingly implicates the conversion of disease-specific proteins into an aggregate-prone b-sheet-rich state as the prime mover of the neurodegenerative process. This prion-like corruptive protein templating or seeding now characterizes such clinically and etiologically diverse neurological disorders as Alzheimer´s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and frontotemporal lobar degeneration. Understanding the misfolding, aggregation, trafficking and pathogenicity of the affected proteins could therefore reveal universal pathomechanistic principles for some of the most devastating and intractable human brain disorders. It is time to accept that the prion concept is no longer confined to prionoses but is a promising concept for the understanding and treatment of a remarkable variety of diseases that afflict primarily our aging society. ​

• Parkinson's disease
• amyloidosis
• prions
• synucleinopathies

• , Dept. Cellular Neurology, University of Tübingen, Tübingen, Germany

  Mathias Jucker

• Fondation IPSEN, Boulogne-Billancourt Cedex, France

  Yves Christen

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