Cerebral stroke is a leading cause of death and persistent disability of elderly in the world. Although
stroke prevention by targeting several risk factors such as diabetes and
hypertension has decreased the
stroke incidence, the total number of
strokes is increasing due to the population aging and new preventive
therapies are needed. Moreover, post-
stroke acute pharmacological strategies aimed to reduce
stroke-induced
brain injury have failed in clinical trials despite being effective in animal models. Finally, approximately 30% of surviving
stroke patients do not recover from
stroke and remain permanently dependent on supportive care in
activities of daily living. Therefore, strategies to improve
stroke recovery in the post-acute phase are highly needed.
Linagliptin is a dipeptidyl peptidase-4 inhibitor which is clinically approved to reduce
hyperglycemia in
type 2 diabetes. The regulation of glycemia by dipeptidyl peptidase-4 inhibition is mainly achieved by preventing endogenous
glucagon-like peptide-1 (GLP-1) degradation. Interestingly,
linagliptin has also shown glycaemia-independent beneficial effects in animal models of
stroke,
Parkinson's disease and
Alzheimer's disease. In some case the preclinical data have been supported with some clinical data. Although potentially very interesting for the development of new strategies against
stroke and
neurodegenerative disorders, the mode of action of
linagliptin in the brain is still largely unknown and seems to occur in a GLP-1R-independent manner. The purpose of this mini-review is to summarize and discuss the recent experimental and clinical work regarding the effects of
linagliptin in the central nervous system, with special emphasis on acute neuroprotection,
stroke prevention and post-
stroke recovery. We also highlight the main questions in this research field that need to be addressed in clinical perspective.