The neurodegeneration in Alzheimer disease and the prion protein

Forloni, Gianluigi; Sclip, Alessandra; Borsello, Tiziana; Balducci, Claudia

doi:10.4161/pri.23286

Cited by 10 publications

(9 citation statements)

References 85 publications

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“…In our hands, the high‐affinity binding of Aβ oligomers to cellular prion protein has been confirmed, but behavioral experiments to evaluate the functional consequence of this interaction did not support a substantial role of prion protein in the Aβ oligomer‐induced neuronal dysfunction . This, however, does not rule out that peptides analogous to the prion sequence could be used to neutralize Aβ oligomer activity in a therapeutic perspective …”

Section: Aβ Oligomersmentioning

confidence: 65%

“…82 This, however, does not rule out that peptides analogous to the prion sequence could be used to neutralize Ab oligomer activity in a therapeutic perspective. 83,84 Kim et al 85 identified 2 new receptors for aggregated Ab, namely, the mouse paired immunoglobulin-like receptor B and its human ortholog, leukocyte immunoglobulin-like receptor. This interaction activates a signaling cascade that affects the neuronal actin cytoskeleton, causing synaptic loss in a mouse model of AD.…”

Section: O L I G O M E R O P a T H I E Smentioning

confidence: 99%

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Oligomeropathies and pathogenesis of Alzheimer and Parkinson's diseases

et al. 2016

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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 Society.

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Section: Aβ Oligomersmentioning

confidence: 65%

Section: O L I G O M E R O P a T H I E Smentioning

confidence: 99%

Oligomeropathies and pathogenesis of Alzheimer and Parkinson's diseases

et al. 2016

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“…[1][2][3][4][5] In these disorders, the abnormal forms of target proteins are essential for pathogenesis. [1][2][3][4][5] In these disorders, the abnormal forms of target proteins are essential for pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effects of NAMI-A-like ruthenium complexes on prion neuropeptide fibril formation

et al. 2015

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Prion diseases are a group of infectious and fatal neurodegenerative disorders caused by the conformational conversion of a cellular prion protein (PrP) into its abnormal isoform PrP(Sc). PrP106-126 resembles PrP(Sc) in terms of physicochemical and biological characteristics and is used as a common model for the treatment of prion diseases. Inhibitory effects on fibril formation and neurotoxicity of the prion neuropeptide PrP106-126 have been investigated using metal complexes as potential inhibitors. Nevertheless, the binding mechanism between metal complexes and the peptide remains unclear. The present study is focused on the interaction of PrP106-126 with NAMI-A and NAMI-A-like ruthenium complexes, including KP418, KP1019, and KP1019-2. Results demonstrated that these ruthenium complexes could bind to PrP106-126 in a distinctive binding mode through electrostatic and hydrophobic interactions. NAMI-A-like ruthenium complexes can also effectively inhibit the aggregation and fibril formation of PrP106-126. The complex KP1019 demonstrated the optimal inhibitory ability upon peptide aggregation, and cytotoxicity because of its large aromatic ligand contribution. The studied complexes could also regulate the copper redox chemistry of PrP106-126 and effectually inhibit the formation of reactive oxygen species. Given these findings, ruthenium complexes with relatively low cellular toxicity may be used to develop potential pharmaceutical products against prion diseases.

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“…This evidence together with genetic studies, identifying AD associated autosomal dominant mutations in the sequence of the amyloid precursor protein (APP) or presenilin 1 and 2 (PS1 and 2) involved in APP metabolism, has attributed to Ab deposits an essential role in AD pathogenesis. In the last decade the small soluble aggregates of Ab, named oligomers, rather than the fibrillar forms, have been considered responsible for the neuronal dysfunction (Benilova et al, 2012;Forloni et al, 2013). Although, synaptotoxic effect of Ab, oligomers is well established in cell culture and transgenic (Tg) animal models of AD, the extent and significance of this effect in humans is unclear.…”

Section: Introductionmentioning

confidence: 99%