Amyloid pore-channel hypothesis: effect of ethanol on aggregation state using frog oocytes for an Alzheimer's disease study

Abstract

Alzheimer's disease severely compromises cognitive function. One of the mechanisms to explain the pathology of Alzheimer’s disease has been the hypotheses of amyloid-pore/channel formation by complex Aβ-aggregates. Clinical studies suggested the moderate alcohol consumption can reduces probability developing neurodegenerative pathologies. A recent report explored the ability of ethanol to disrupt the generation of complex Aβ in vitro and reduce the toxicity in two cell lines. Molecular dynamics simulations were applied to understand how ethanol blocks the aggregation of amyloid. On the other hand, the in silico modeling showed ethanol effect over the dynamics assembling for complex Aβ-aggregates mediated by break the hydrosaline bridges between Asp 23 and Lys 28, was are key element for amyloid dimerization. The amyloid pore/channel hypothesis has been explored only in neuronal models, however recently experiments suggested the frog oocytes such an excellent model to explore the mechanism of the amyloid pore/channel hypothesis. So, the used of frog oocytes to explored the mechanism of amyloid aggregates is new, mainly for amyloid/pore hypothesis. Therefore, this experimental model is a powerful tool to explore the mechanism implicates in the Alzheimer’s disease pathology and also suggests a model to prevent the Alzheimer’s disease pathology. [BMB Reports 2015; 48(1): 13-18]

Beneficial effects of Panax ginseng for the treatment and prevention of neurodegenerative diseases: past findings and future directions

“…While the pathogenic mechanism of human Parkinson's disease is still not fully understood, oxidative stress and cytotoxicity are thought to play an important role in the degeneration of dopaminergic neurons [63] , [64] , [69] , [70] , [71] , [72] , [73] , [74] . Mechanistically, it is known that dopamine neurotransmitter is chemically labile and its oxidation products, such as dopamine quinones and semiquinones, are highly cytotoxic to neurons in general and dopaminergic neurons in particular [63] , [64] , [69] .…”

In vitro assessment of selected Korean plants for antioxidant and antiacetylcholinesterase activities

“…Considering AD’s complex multifactorial etiology, phytochemicals that have antioxidant as well as AChE inhibitory activity have been considered to be safer and better therapeutic candidates for treating AD (Parodi et al. 2015 ). Antioxidant therapy has proven successful for improving cognitive function and behavioral deficits in patients with mild to moderate AD (Gutzmann and Hadler 1998 ).…”

Amyloids: Regulators of Metal Homeostasis in the Synapse

“…Studies by others and our group suggest that AβPs directly incorporate into the membrane and form channels (pores) that allow the passage of Ca 2+ and other cations, and that the resulting change in [Ca 2+ ] i may be a primary pathogenetic event in AβP neurotoxicity [110][111][112]. Neurotoxic peptide fragments of AβP, including AβP(1-40), AβP (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) and AβP , have been demonstrated to incorporate into artificial planar lipid membranes and form giant multi-level pores (~5 nS) with cation (including Ca 2+ ) selectivity [113][114][115].…”

“…PrP C reportedly binds four Cu atoms in the octarepeat domain (-PHGGGWGQ-) in its N-terminal. Cu can also bind to His 96 and His 111 [69]. Huang et al found that PrP C binds to α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type and/or NMDA-type glutamate receptors and affects their function in a Cu-dependent manner [70].…”