Link between Cancer and Alzheimer Disease via Oxidative Stress Induced by Nitric Oxide-Dependent Mitochondrial DNA Overproliferation and Deletion

Abstract

Nitric oxide- (NO-) dependent oxidative stress results in mitochondrial ultrastructural alterations and DNA damage in cases of Alzheimer disease (AD). However, little is known about these pathways in human cancers, especially during the development as well as the progression of primary brain tumors and metastatic colorectal cancer. One of the key features of tumors is the deficiency in tissue energy that accompanies mitochondrial lesions and formation of the hypoxic smaller sized mitochondria with ultrastructural abnormalities. We speculate that mitochondrial involvement may play a significant role in the etiopathogenesis of cancer. Recent studies also demonstrate a potential link between AD and cancer, and anticancer drugs are being explored for the inhibition of AD-like pathology in transgenic mice. Severity of the cancer growth, metastasis, and brain pathology in AD (in animal models that mimic human AD) correlate with the degree of mitochondrial ultrastructural abnormalities. Recent advances in the cell-cycle reentry of the terminally differentiated neuronal cells indicate that NO-dependent mitochondrial abnormal activities and mitotic cell division are not the only important pathogenic factors in pathogenesis of cancer and AD, but open a new window for the development of novel treatment strategies for these devastating diseases.

The Mechanism of Memory Enhancement of Acteoside (Verbascoside) in the Senescent Mouse Model Induced by a Combination of d‐gal and AlCl3

“…Measurement of levels of cleaved caspase‐3 and caspase‐2 will be carried out in future experiments to confirm this. NO is an important physiological signalling agent, but high concentrations can result in oxidative damage (Aliev et al ., ). It has been implicated in pathological processes associated with several neurodegenerative disorders including AD (Santos et al ., ).…”

Protein Misfolding and Aggregation in Alzheimer’s Disease and Type 2 Diabetes Mellitus

“…These intracellular conformationally twisted fibres of tau protein impair axonal transport between the cell body and numerous synapses, which is crucial to neuronal function and survival [30–32]. Concomitantly, nitric oxide dependent oxidative stress leads to mitochondrial energy deprivation in AD [33]. …”

Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence

“…Sustained cerebral hypoperfusion can impair endothelial mitochondrial oxidative function, resulting in increased synthesis of endothelial ROS [219-222]. ROS can in turn promote eNOS uncoupling, leading to reduced vasodilatory endothelial NO levels and cerebral hypoperfusion in a positive feedback loop [54,55,182,206].…”