Focus on the Complex Interconnection between Cancer, Narcolepsy and Other Neurodegenerative Diseases: A Possible Case of Orexin-Dependent Inverse Comorbidity - PubMed (original) (raw)
Review
Focus on the Complex Interconnection between Cancer, Narcolepsy and Other Neurodegenerative Diseases: A Possible Case of Orexin-Dependent Inverse Comorbidity
Maria P Mogavero et al. Cancers (Basel). 2021.
Abstract
Conditions such as Alzheimer's (AD) and Parkinson's diseases (PD) are less prevalent in cancer survivors and, overall, cancer is less prevalent in subjects with these neurodegenerative disorders. This seems to suggest that a propensity towards one type of disease may decrease the risk of the other. In addition to epidemiologic data, there is also evidence of a complex biological interconnection, with genes, proteins, and pathways often showing opposite dysregulation in cancer and neurodegenerative diseases. In this narrative review, we focus on the possible role played by orexin signaling, which is altered in patients with narcolepsy type 1 and in those with AD and PD, and which has been linked to β-amyloid brain levels and inflammation in mouse models and to cancer in cell lines. Taken together, these lines of evidence depict a possible case of inverse comorbidity between cancer and neurodegenerative disorders, with a role played by orexins. These considerations suggest a therapeutic potential of orexin modulation in diverse pathologies such as narcolepsy, neurodegenerative disorders, and cancer.
Keywords: cancer; inverse comorbidity; narcolepsy; neurodegeneration; orexin.
Conflict of interest statement
The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
Figures
Figure 1
Schematic representation of the bidirectional interactions between cancer and neurodegenerative diseases and their modulatory processes. Neurodegenerative diseases and cancer are framed as two sets of disorders with “too much” or “too little” apoptosis, respectively. Reactive oxygen species (ROS), alterations in proteostasis, and microRNA (miRNAs) are among the key factors that may underlie the differences between the two sets of disorders. Some of the specific molecular mechanisms thought to be involved in this pattern of inverse comorbidity are highlighted in the middle column (see the text of the paper for abbreviations). ↓ = downregulated, ↑ = upregulated.
Figure 2
Schematic representation of the possible role of superoxide dismutase (SOD1) in amyothrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and cancer metastasis. See the text of the paper for abbreviations. ↓ = decrease, ↑ = increase, ⊕ = stimulation.
Figure 3
Schematic representation of the signaling potential of orexin receptors, as demonstrated by experiments on recombinant cell lines. Continuous arrows indicate demonstrated or hypothesized causal links between messengers and/or enzymes. The broken arrow indicates an undetermined causal pathway. GPCR: G-protein coupled receptors. AC: adenylate cyclase. PLC, PLA2, PLD: phospholipase C, A2, and D, respectively. NSCCs: non-selective cation channels. 2-AC: 2-acyl-glycerol. CB1R: cannabinoid type 1 receptor. See the text of the paper for the other abbreviations.
Figure 4
Schematic representation of the possible mechanisms underlying the role of orexin and its influences on neurodegeneration and cancer. See the text of the paper for abbreviations. ↓ = decrease, ↑ = increase.