path(HBP:"mitochondrial dysfunction")
Arora et al. (2013) investigated, in a cellular system, the effect of prolonged Abeta exposure on nAChR function. The rodent neuroblastoma cell line NG108-15 was transfected with alpha4beta2 nAChRs and treated for three days with 100 nM Abeta. The following acute stimulation with Abeta and nicotine led to receptor activation that caused a perturbation of intracellular calcium homeostasis followed by mitochondrial dysfunction and increased oxidative stress (Arora et al., 2013) PubMed:25514383
In mechanistic studies, it was proposed that methylene blue inhibits the Aβ-ABAD interaction and decreases mitochondrial dysfunction by decreasing the expression of ABAD levels, in addition to decreasing Aβ levels. PubMed:30444369
Mitochondrial dysfunction is the hallmark of Aβ-induced toxicity. 50-52 PubMed:30444369
Mitochondria are instrumental in the regulation of energy metabolism, and impairment in mitochondrial function has been implicated in the pathogenesis of AD, leading to the mitochondrial cascade hypothesis of AD [121]. PubMed:29758300
Altogether, as with proteinopathy, accumulation of damaged or dysfunctional mitochondria is detrimental to the development of AD pathologies PubMed:29758300
Dysfunctional mitochondria are critically harmful to cells, as this leads to decreased synthesis of cellular ATP and accumulation of ROS, which further overburden and damage other functional mitochondria. PubMed:29758300
Dysfunctional mitochondria are critically harmful to cells, as this leads to decreased synthesis of cellular ATP and accumulation of ROS, which further overburden and damage other functional mitochondria. PubMed:29758300
Previous studies demonstrate impaired mitochondrial function preceding the accumulation of hallmark proteins in AD, such as Aβ [123,124] and tau [125]. PubMed:29758300
Previous studies demonstrate impaired mitochondrial function preceding the accumulation of hallmark proteins in AD, such as Aβ [123,124] and tau [125]. PubMed:29758300
Thus, as a quality control mechanism, mitophagy − a form of selective macroautophagy that specifically targets mitochondria − occurs in response to damaged or dysfunctional mitochondria in order to prevent mitochondrial bioenergetic deficits. PubMed:29758300
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.