Antioxidant SkQ1 Alleviates Signs of Alzheimer's Disease-like Pathology in Old OXYS Rats by Reversing Mitochondrial Deterioration

Abstract

According to our past and present results, the repair of the mitochondrial apparatus by SkQ1 is a promising strategy against AD.

SkQ1 Suppresses the p38 MAPK Signaling Pathway Involved in Alzheimer’s Disease-Like Pathology in OXYS Rats

“…Indeed, the prolonged supplementation with SkQ1 in our experiment slowed down the accumulation of pathological Aβ in the OXYS rat hippocampus. Similar results about the treatment and prevention of AD-like pathology by SkQ1 have been obtained in several other studies on SkQ1's effects on the dynamics of neurodegenerative changes in OXYS rats [11,13,15]. In addition, these studies have revealed that this drug reduced the overall level of the hyperphosphorylated tau protein, owing to a decrease in its phosphorylation on MAPK-dependent sites [13,15].…”

“…Previously, we have shown that SkQ1 [10] at nanomolar concentrations can prevent, slow down, or partially alleviate AD-like pathology in accelerated-senescence OXYS rats [11,12]. The nontransgenic OXYS rat strain is characterized by spontaneously developing key signs of AD in humans [13].…”

Prevention of Cognitive Decline in Alzheimer’s Disease by Novel Antioxidative Supplements

“…Plastoquinonyl-decyltriphenylphosphonium (SkQ1), mitoquinone mesylate (MitoQ) and astaxanthin are mitochondria-targeted antioxidants [127,128]. SkQ1 increased behavioral activity, and reduced destructive changes in mitochondria, pathological accumulation of AβPP, Aβ, hyperphosphorylation of tau-protein and hippocampal Aβ 40 and Aβ 42 protein levels in AD model rats [129,130]. MitoQ attenuated Aβ-neurotoxicity in the cortical neuron and prevented increased production of ROS, loss of mitochondrial membrane potential, cognitive decline, Aβ accumulation, astrogliosis, synaptic loss and caspase activation in AD model mice [131].…”

Alzheimer’s Disease: Molecular Hallmarks and Yeast Models

“…Moreover, oxidative stress is also the major cause of glial inflammation and apoptosis. All these findings suggest a critical role for oxidative stress in promoting AD and highlight the for antioxidants as potential drugs for combating AD [17][18][19][20][21][22][23].…”

“…Evidence is presented suggesting amyloid oligomers as necessary but insufficient causes of the dementia and that, for dementia to develop, additional cofactors are required [13]. Those cofactors include several subcellular processes including oxidative damage [10,[14][15][16][17][18][19][20][21][22][23], recruitment of peripheral immune cells and excessive production of pro-inflammatory mediators [10,[24][25][26][27][28][29], mitochondrial impairments and chronic energy imbalance [12,20,[30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47], chronic endoplasmic reticulum (ER) stress [48] and autophagy dysfunction [22,[49][50][51][52][53][54], the abnormality and dysfunction of MAM (the mitocho...…”