Prospective epidemiological studies suggest that type 2 diabetes is a risk factor for neurodegenerative
pathologies such as Alzheimer disease, vascular dementia, and Parkinson disease. Drugs
that act as incretin receptor agonists or inhibit the proteolytic degradation of incretins (dipeptidyl peptidase
4 inhibitors) have been approved since 2005 for use in diabetes treatment. Dipeptidyl peptidase
4 (DPP4) cleaves N-terminal dipeptides from polypeptides when the second residue is proline, hydroxyproline,
dehydroproline or alanine. The inhibition of DPP4 hydrolytic activities extends the halflife
of these peptides by preventing their degradation. Several peptides have been identified as DPP4
substrates, including neuropeptides, chemokines, and the incretin hormones; hence the pleomorphic effects
of DPP4 inhibition. Recently, the neuroprotective properties of these drugs have been evaluated in cell cultures and
animal models, not yet in human trials. Although mechanisms distinct from glycaemic control alone have been claimed to
account for protection against neuronal degeneration, the precise cellular mechanism by which DPP4 inhibitors exert their
neuroprotective effects remain unknown. The present review is focused on the candidate pathways that could be involved
in mediating DPP4 inhibitors-mediated protection against neuronal degeneration.
Keywords: Alzheimer disease, diabetes mellitus, dipeptidyl peptidase 4 inhibitors, Parkinson disease, vascular dementia.
Rights & PermissionsPrintExport