Abstract
Diabetes affects more than 425 million people worldwide, a scale approaching pandemic proportion. Diabetes represents a major risk factor for stroke, and therefore is actively addressed for stroke prevention. However, how diabetes affects stroke severity has not yet been extensively considered, which is surprising given the evident but understudied common mechanistic features of both pathologies. The increase in number of diabetic people, incidence of stroke in the presence of this specific risk factor, and the exacerbation of ischemic brain damage in diabetic conditions (at least in animal models) warrants the need to integrate this comorbidity in preclinical studies of brain ischemia to develop novel therapeutic approaches. Therefore, a better understanding of the commonalties involved in the course of both diseases would offer the promise of discovering novel neuroprotective pathways that would be more appropriated to clinical scenarios. In this article, we will review the relevant mechanisms that have been identified as common traits of both pathologies and that could be, to our knowledge, potential targets in both pathologies.
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Abbreviations
- ACE inhibitors:
-
Angiotensin converting enzyme inhibitors
- ADA:
-
American diabetes association
- Akt:
-
Serine–threonine kinase
- ARBs:
-
Angiotensin II receptor blockers
- ATF3:
-
Activating transcription factor 3
- ATP:
-
Adenosine triphosphate
- CamK:
-
Ca2+/calmodulin kinase
- CaMKK:
-
CaM kinase kinase
- cAMP:
-
Cyclic adenosine monophosphate
- CNS:
-
Central nervous system
- CREB:
-
C-AMP response element-binding protein
- CRP:
-
C-reactive protein
- DPP-4:
-
Dipeptidyl peptidase-4
- FFA:
-
Free fatty acid
- GLP-1:
-
Glucagon-like peptide-1
- HbA1c:
-
Hemoglobin A1c
- HDL:
-
High-density lipoproteins
- ICER:
-
Inducible cAMP early repressor
- IL1-β:
-
Interleukin1-beta
- JNKs:
-
c-Jun N-terminal kinases
- LDL:
-
Low-density lipoproteins
- NGF:
-
Nerve growth factor
- NMDA:
-
N-methyl-D-aspartate
- PDE:
-
Phosphodiesterase
- PKA:
-
Protein kinase A
- PKB:
-
Protein kinase B
- PKCδ:
-
Protein kinase Cdelta
- ROS:
-
Reactive oxygen species
- SGLT-2:
-
Sodium-glucose co-transporter-2
- STAIR:
-
Stroke therapy academic industry roundtable
- TNF:
-
Tumor necrosis factor
- VADT:
-
Veterans affairs diabetes trial
- VLDL:
-
Very low-density lipoproteins
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Acknowledgements
The authors thank all their past and present team members and collaborators who have contributed to the data discussed in the review. We would like to express our gratitude to Drs. Heurteaux and Mazzela for their cordial support, valuable information, and guidance, which helped us in completing this review.
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This work was funded by the Centre National de la Recherche Scientifique - CNRS.
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Coppola, T., Beraud-Dufour, S., Lebrun, P. et al. Bridging the Gap Between Diabetes and Stroke in Search of High Clinical Relevance Therapeutic Targets. Neuromol Med 21, 432–444 (2019). https://doi.org/10.1007/s12017-019-08563-5
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DOI: https://doi.org/10.1007/s12017-019-08563-5