Oligomeropathies and pathogenesis of Alzheimer and Parkinson's diseases
- 31 March 2016
- journal article
- review article
- Published by Wiley in Movement Disorders
- Vol. 31 (6), 771-781
- https://doi.org/10.1002/mds.26624
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. © 2016 International Parkinson and Movement Disorder SocietyKeywords
This publication has 152 references indexed in Scilit:
- Direct Observation of the Interconversion of Normal and Toxic Forms of α-SynucleinCell, 2012
- Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-βNature, 2012
- Cognitive effects of cell-derived and synthetically derived Aβ oligomersNeurobiology of Aging, 2011
- Amyloid-β forms fibrils by nucleated conformational conversion of oligomersNature Chemical Biology, 2011
- Reversing EphB2 depletion rescues cognitive functions in Alzheimer modelNature, 2010
- Reduced expression of peroxisome-proliferator activated receptor gamma coactivator-1α enhances α-synuclein oligomerization and down regulates AKT/GSK3β signaling pathway in human neuronal cells that inducibly express α-synucleinNeuroscience Letters, 2010
- Cellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomersNature, 2009
- Protection of synapses against Alzheimer's-linked toxins: Insulin signaling prevents the pathogenic binding of Aβ oligomersProceedings of the National Academy of Sciences of the United States of America, 2009
- Dopamine neurons implanted into people with Parkinson's disease survive without pathology for 14 yearsNature Medicine, 2008
- Applicability of current staging/categorization of α-synuclein pathology and their clinical relevanceActa Neuropathologica, 2008