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Review
. 2023 Jul 24;12(7):1042.
doi: 10.3390/biology12071042.

Exploring Rosiglitazone's Potential to Treat Alzheimer's Disease through the Modulation of Brain-Derived Neurotrophic Factor

Mackayla L Nelson  1 , Julia A Pfeifer  1 , Jordan P Hickey  1 , Andrila E Collins  1 , Bettina E Kalisch  1
Affiliations
Review

Exploring Rosiglitazone's Potential to Treat Alzheimer's Disease through the Modulation of Brain-Derived Neurotrophic Factor

Mackayla L Nelson et al. Biology (Basel). .

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that debilitates over 55 million individuals worldwide. Currently, treatments manage and alleviate its symptoms; however, there is still a need to find a therapy that prevents or halts disease progression. Since AD has been labeled as "type 3 diabetes" due to its similarity in pathological hallmarks, molecular pathways, and comorbidity with type 2 diabetes mellitus (T2DM), there is growing interest in using anti-diabetic drugs for its treatment. Rosiglitazone (RSG) is a peroxisome proliferator-activated receptor-gamma agonist that reduces hyperglycemia and hyperinsulinemia and improves insulin signaling. In cellular and rodent models of T2DM-associated cognitive decline and AD, RSG has been reported to improve cognitive impairment and reverse AD-like pathology; however, results from human clinical trials remain consistently unsuccessful. RSG has also been reported to modulate the expression of brain-derived neurotrophic factor (BDNF), a protein that regulates neuroplasticity and energy homeostasis and is implicated in both AD and T2DM. The present review investigates RSG's limitations and potential therapeutic benefits in pre-clinical models of AD through its modulation of BDNF expression.

Keywords: Alzheimer’s disease; brain-derived neurotrophic factor; clinical trials; peroxisome proliferator-activated receptor-gamma; review; rosiglitazone; type 2 diabetes mellitus.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of brain-derived neurotrophic factor (BDNF) formation, processing, secretion and receptor activation. Created with BioRender.com (accessed on 30 April 2023).
Figure 2
Figure 2
Rosiglitazone (RSG) modulating the expression of neural brain-derived neurotrophic factor (BDNF) through [1] peroxisome proliferator-activated receptor-gamma (PPARγ)-mediated transcriptional regulation and [2] upregulation of the cyclic AMP-response element binding protein (CREB)/BDNF/tropomyosin receptor kinase B (TrkB) pathway. Created with BioRender.com (accessed 30 April 2023, license agreement: KA25B75AY7).
See this image and copyright information in PMC

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