Despite an ever-growing prevalence and increasing economic burden of Alzheimer’s disease (AD) and Parkinson’s disease (PD), recent advances in drug development have only resulted in minimally effective treatment. In AD, along with amyloid and tau phosphorylation, there is an associated increase in inflammation/glial activation, a decrease in synaptic function, an increase in astrocyte activation, and a state of insulin resistance. In PD, along with α-synuclein accumulation, there is associated inflammation, synaptic dysfunction, dopaminergic neuronal loss, and some data to suggest insulin resistance. Therapeutic strategies for neurodegenerative disorders have commonly targeted individual pathological processes. An effective treatment might require either utilization of multiple drugs which target the individual pathological processes which underlie the neurodegenerative disease or the use of a single agent which could influence multiple pathological processes. Insulin and incretins are compounds with multiple effects on neurodegenerative processes. Preclinical studies have demonstrated that GLP-1 receptor agonists reduce neuroinflammation, reduce tau phosphorylation, reduce amyloid deposition, increase synaptic function, and improve memory formation. Incretin mimetics may act through the restoration of insulin signaling pathways, inducing further neuroprotective effects. Currently, phase 2 and phase 3 trials are underway in AD and PD populations. Here, we provide a comprehensive review of the therapeutic potential of incretin mimetics and insulin in AD and PD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.