Oligomer Formation and Cross-Seeding: The New Frontier

Kathleen Farmer, Julia E. Gerson, Rakez Kayed

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The accumulation of protein aggregates in the brain is a defining feature of a number of neurodegenerative diseases. Though diseases vary in the composition of aggregated proteins (amyloid-β and tau are primarily implicated in Alzheimer's disease, α-synuclein is the primary protein aggregate in Parkinson's disease, etc.), similarities in the formation of soluble intermediate aggregates, some of which go on to deposit in stable fibrillar structures, suggests that the protein sequence may be far less important than the aggregate conformation to toxicity and onset of disease. Growing evidence suggests that intermediate or independently formed oligomeric aggregates are more highly toxic than fibrils, and are more efficient seeds for the aggregation of endogenous protein. Furthermore, the overlap of different aggregated proteins in disease, as well as the ability of amyloid oligomers to cross-seed the aggregation of each other, suggests that synergistic interactions between varying aggregant proteins is a critical component in neurodegeneration. The progression of aggregates along defined pathways throughout the brain is crucial to the spread of disease and likely depends upon the transport of aggregates from affected to unaffected brain regions. Thus, the presence of oligomeric seeds that more efficiently seed the aggregation of homologous and diverse proteins may underlie neurodegeneration.

Original languageEnglish (US)
JournalIsrael Journal of Chemistry
DOIs
StateAccepted/In press - 2016

Fingerprint

Oligomers
Seed
Brain
Agglomeration
Proteins
Synucleins
Neurodegenerative diseases
Amyloidogenic Proteins
tau Proteins
Poisons
Amyloid
Toxicity
Conformations
Deposits
Chemical analysis

Keywords

  • Aggregation
  • Neurochemistry
  • Oligomers
  • Protein folding

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Oligomer Formation and Cross-Seeding : The New Frontier. / Farmer, Kathleen; Gerson, Julia E.; Kayed, Rakez.

In: Israel Journal of Chemistry, 2016.

Research output: Contribution to journalArticle

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