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Link between cancer and Alzheimer disease via oxidative stress induced by nitric oxide-dependent mitochondrial DNA overproliferation and deletion.

Aliev G, Obrenovich ME, Tabrez S, Jabir NR, Reddy VP, Li Y, Burnstock G, Cacabelos R, Kamal MA - Oxid Med Cell Longev (2013)

Bottom Line: Nitric oxide- (NO-) dependent oxidative stress results in mitochondrial ultrastructural alterations and DNA damage in cases of Alzheimer disease (AD).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.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.

View Article: PubMed Central - PubMed

Affiliation: GALLY International Biomedical Research Consulting LLC, 7733 Louis Pasteur Drive, No. 328, San Antonio, TX 78229, USA. aliev03@gmail.com

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.

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Related in: MedlinePlus

The schematic drawing pattern of the GRK2 overexpression that most likely appeared to be as a compensatory to the hypoxia and hypoperfusion induced oxidative stress that initiates the development and maturation of AD. Modified and reprinted with permission of CNS Neurol Disord Drug Targets [92].
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fig2: The schematic drawing pattern of the GRK2 overexpression that most likely appeared to be as a compensatory to the hypoxia and hypoperfusion induced oxidative stress that initiates the development and maturation of AD. Modified and reprinted with permission of CNS Neurol Disord Drug Targets [92].

Mentions: Some of us and others [35–38] have also found a critical role of GRK2 in the endothelin signaling cascade and many of the effects of ET-1 on cancer may be mediated by GRK2 (Figure 2). In this regard, it is important to note the importance of GRK2 on ET-1 receptors, downstream events, and its relationship with cancer. The importance of the strong immunologic relationship to most cancers is illustrated in part by high expression of GRK2 in different cellular types of the immune system. This emerges as an important regulator of cell responses during inflammation, such as leukocyte trafficking to the inflammatory foci, T-cell egression from lymphoid organs, leukocyte activation, or proliferation [39]. GRK2 is known to phosphorylate chemokines and chemotactic receptors for CCR5, CCR2b, CXCR4, CXCR2, and substance P, S1P or formyl-peptide, respectively [39].


Link between cancer and Alzheimer disease via oxidative stress induced by nitric oxide-dependent mitochondrial DNA overproliferation and deletion.

Aliev G, Obrenovich ME, Tabrez S, Jabir NR, Reddy VP, Li Y, Burnstock G, Cacabelos R, Kamal MA - Oxid Med Cell Longev (2013)

The schematic drawing pattern of the GRK2 overexpression that most likely appeared to be as a compensatory to the hypoxia and hypoperfusion induced oxidative stress that initiates the development and maturation of AD. Modified and reprinted with permission of CNS Neurol Disord Drug Targets [92].
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3649749&req=5

fig2: The schematic drawing pattern of the GRK2 overexpression that most likely appeared to be as a compensatory to the hypoxia and hypoperfusion induced oxidative stress that initiates the development and maturation of AD. Modified and reprinted with permission of CNS Neurol Disord Drug Targets [92].
Mentions: Some of us and others [35–38] have also found a critical role of GRK2 in the endothelin signaling cascade and many of the effects of ET-1 on cancer may be mediated by GRK2 (Figure 2). In this regard, it is important to note the importance of GRK2 on ET-1 receptors, downstream events, and its relationship with cancer. The importance of the strong immunologic relationship to most cancers is illustrated in part by high expression of GRK2 in different cellular types of the immune system. This emerges as an important regulator of cell responses during inflammation, such as leukocyte trafficking to the inflammatory foci, T-cell egression from lymphoid organs, leukocyte activation, or proliferation [39]. GRK2 is known to phosphorylate chemokines and chemotactic receptors for CCR5, CCR2b, CXCR4, CXCR2, and substance P, S1P or formyl-peptide, respectively [39].

Bottom Line: Nitric oxide- (NO-) dependent oxidative stress results in mitochondrial ultrastructural alterations and DNA damage in cases of Alzheimer disease (AD).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.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.

View Article: PubMed Central - PubMed

Affiliation: GALLY International Biomedical Research Consulting LLC, 7733 Louis Pasteur Drive, No. 328, San Antonio, TX 78229, USA. aliev03@gmail.com

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.

Show MeSH
Related in: MedlinePlus