Insulin and
Insulin Growth Factor-1 (IGF-1) play a major role in body homeostasis and
glucose regulation. They also have paracrine/autocrine functions in the brain. The
Insulin/IGF-1 signaling pathway contributes to the control of neuronal excitability, nerve cell metabolism and cell survival.
Glucagon like peptide-1 (GLP-1), known as an insulinotropic
hormone has similar functions and growth like properties as
insulin/IGF-1. Growing evidence suggests that dysfunction of these pathways contribute to the progressive loss of neurons in
Alzheimer's disease (AD) and
Parkinson's disease (PD), the two most frequent
neurodegenerative disorders. These findings have led to numerous studies in preclinical models of
neurodegenerative disorders targeting
insulin/IGF-1 and
GLP-1 signaling with currently available anti-diabetics. These studies have shown that administration of
insulin,
IGF-1 and
GLP-1 agonists reverses signaling abnormalities and has positive effects on
surrogate markers of neurodegeneration and behavioral outcomes. Several proof-of-concept studies are underway that attempt to translate the encouraging preclinical results to patients suffering from AD and PD. In the first part of this review, we discuss physiological functions of
insulin/IGF-1 and
GLP-1 signaling pathways including downstream targets and receptors distribution within the brain. In the second part, we undertake a comprehensive overview of preclinical studies targeting
insulin/IGF-1 or
GLP-1 signaling for treating AD and PD. We then detail the design of clinical trials that have used anti-diabetics for treating AD and PD patients. We close with future considerations that treat relevant issues for successful translation of these encouraging preclinical results into treatments for patients with AD and PD.