MA-[d-Leu-4]-OB3, a Small Molecule Synthetic Peptide Leptin Mimetic, Mirrors the Cognitive Enhancing Action of Leptin in a Mouse Model of Type 1 Diabetes Mellitus and Alzheimer’s Disease-Like Cognitive Impairment

MA-[D-Leu-4]-OB3, a small molecule synthetic peptide leptin mimetic, improves episodic memory, and reduces serum levels of tumor necrosis factor-alpha and neurodegeneration in mouse models of Type 1 and Type 2 Diabetes Mellitus

“…In this regard, links between defective insulin signaling, AD, and inflammation are wellestablished (de Oliveira Santos et al, 2012;Ferreira et al, 2014;El Khoury et al, 2014;De Felice and Ferreira, 2014;Ferreira et al, 2018). The observed ability of MA-[D-Leu-4]-OB3 to improve insulin sensitivity peripherally and in the brain, and to enhance episodic memory in mouse models of both T1DM (Anderson et al, 2019) and T2DM (Hirschstein et al, 2019), prompted us to expand our investigation of the actions of MA-[D-Leu-4]-OB3 to include an examination of its effects on the modulation of one or more pro-inflammatory cytokines known to enhance neurodegeneration, and on histopathological changes in the hippocampus and cerebral cortex in these mouse models.…”

“…Our laboratory has recently shown that MA-[D-Leu-4]-OB3, a small molecule synthetic peptide leptin mimetic, crosses the blood-brain barrier (Anderson et al, 2017), reduces body weight gain (Wang et al, 2018), improves insulin sensitivity (Wang et al, 2018;Anderson et al, 2019;Hirschstein et al, 2019), and normalizes episodic memory in mouse models of T1DM (Anderson et al, 2019) and T2DM (Hirschstein et al, 2019). In the present study, we hypothesized that the observed ability of MA-[D-Leu-4]-OB3 to improve cognitive function may be influenced not only by its effects on glycemic control, but also by actions associated with reducing serum concentrations of pro-inflammatory cytokines known to be associated with neuronal degeneration.…”

Harnessing the Power of Leptin: The Biochemical Link Connecting Obesity, Diabetes, and Cognitive Decline

“…Because the links between obesity, diabetes, and cognitive impairment are strong, and the regulatory effects of our synthetic peptide leptin mimetics on energy balance and glucose homeostasis have been established in a number of mouse models of obesity and diabetes, it was of interest to examine whether their influence on cognitive function also mimicked that of leptin. In STZ-treated Swiss Webster mice, a model of insulin deficiency (Anderson et al, 2019), and in DIO mice, a model of insulin resistance (Hirschstein et al, 2019), oral delivery of MA-[D-Leu-4]-OB3 in Intravail R not only reduced body weight gain and restored glycemic control, but also improved episodic memory.…”

Nanomedicine: A Promising Way to Manage Alzheimer’s Disease

“…Recent findings have revealed the associations between high sugar level and AD development. It has been found that MA-[D-leu-4]-OB3 used for the treatment of obesity and diabetes can relieve AD pathologies (Anderson et al, 2019). About the association of AD and diabetes mellitus type 2 (T2DM), a study has reported that the depletion of caveolin-1 in T2DM can induce AD (Bonds et al, 2019).…”