Inhibitors of α-synuclein oligomerization and toxicity: A future therapeutic strategy for Parkinson's disease and related disorders

Dena A.M. Amer, G. Brent Irvine, Omar Ali El-Agnaf

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

An abundance of genetic, histopathological, and biochemical evidence has implicated the neuronal protein, α-synuclein (α-syn) as a key player in the development of several neurodegenerative diseases, the so-called synucleinopathies, of which Parkinson's disease (PD) is the most prevalent. Development of disease appears to be linked to events that increase the intracellular concentration of α-syn or cause its chemical modification, either of which can accelerate the rate at which it forms aggregates. Examples of such events include increased copy number of genes, decreased rate of degradation via the proteasome or other proteases, or altered forms of α-syn, such as truncations, missense mutations, or chemical modifications by oxidative reactions. Aggregated forms of the protein, especially newly formed soluble aggregates, are toxic to cells, so that one therapeutic strategy would be to reduce the rate at which such oligomerization occurs. We have therefore designed several peptides and also identified small molecules that can inhibit α-syn oligomerization and toxicity in vitro. These compounds could serve as lead compounds for the design of new drugs for the treatment of PD and related disorders in the future.

Original languageEnglish
Pages (from-to)223-233
Number of pages11
JournalExperimental Brain Research
Volume173
Issue number2
DOIs
Publication statusPublished - Aug 2006
Externally publishedYes

Fingerprint

Synucleins
Parkinson Disease
Gene Dosage
Poisons
Drug Design
Missense Mutation
Proteasome Endopeptidase Complex
Neurodegenerative Diseases
Molecular Biology
Proteins
Peptide Hydrolases
Peptides
Therapeutics

Keywords

  • α-Synuclein
  • Amyloid fibrils
  • Beta-sheet breaker peptides
  • Drug discovery
  • Neurodegenerative diseases

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Inhibitors of α-synuclein oligomerization and toxicity : A future therapeutic strategy for Parkinson's disease and related disorders. / Amer, Dena A.M.; Irvine, G. Brent; Ali El-Agnaf, Omar.

In: Experimental Brain Research, Vol. 173, No. 2, 08.2006, p. 223-233.

Research output: Contribution to journalArticle

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