Oligomeropathies and pathogenesis of Alzheimer and Parkinson's diseases

Gianluigi Forloni, Vladimiro Artuso, Pietro La Vitola, Claudia Balducci

Research output: Contribution to journalArticle

Abstract

The term oligomeropathies defines the neurodegenerative disorders associated with protein misfolding, where small soluble aggregates (oligomers 4-200 KDa) are the cause of neuronal dysfunction and are responsible for spreading the pathology. The ability of these soluble β-sheet conformers to induce neuronal damage has been investigated in direct challenge with the monomeric and fibrillary structures, showing that only the oligomeric species affected the neurons. β amyloid oligomers were initially purified from Alzheimer brains and obtained using synthetic peptides. Together with the neuronal death, synaptic dysfunction, loss of spines, and LTP impairment were seen with the direct application of β amyloid oligomers. Similar results have been described with proteins associated with other neurodegenerative disorders. The biological activities of oligomeric forms of α synuclein have been described in Parkinson's disease and Lewy body dementia. Detrimental effects have been associated with the oligomeric forms of prion, tau, and huntingtin, the key proteins in prion diseases, frontotemporal dementia, and Huntington's disease, respectively. The molecular mechanisms of the oligomer-related toxic effects can be summarized under three headings: nonspecific perturbance of cellular and intracellular membranes, specific interaction with various cellular entities, and amyloid pore channel formation. To characterize and distinguish oligomer actions better, we compared the ability of β amyloid and α synuclein oligomers to induce cognitive impairment when applied directly into the brain in the same acute mouse model. We also investigated the role of inflammatory components.

Original languageEnglish
Pages (from-to)771-781
JournalMovement Disorders
Volume31
DOIs
Publication statusPublished - 2016

Keywords

  • Aggregation
  • Alpha synuclein
  • Beta amyloid
  • Neurodegeneration
  • Spreading

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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