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Title: Exploring the link between Parkinson's disease and type 2 diabetes mellitus in Drosophila
Authors: Sanz, Francisco José
Solana‐Manrique, Cristina
Lilao Garzón, Joaquín 
Brito Casillas, Yeray 
Muñoz Descalzo, Silvia 
Paricio, Nuria
UNESCO Clasification: 32 Ciencias médicas
3201 Ciencias clínicas
3209 Farmacología
Keywords: Drosophila
High fat/sugar diet
Mouse model
Parkinson's disease, et al
Issue Date: 2022
Project: Caracterización molecular de la organización tridimensional de células durante la embriogénesis temprana en ratones y humanos 
Journal: FASEB Journal 
Abstract: Parkinson's disease (PD) is the second most common neurodegenerative disease. Diabetes mellitus (DM) is a metabolic disease characterized by high levels of glucose in blood. Recent epidemiological studies have highlighted the link between both diseases; it is even considered that DM might be a risk factor for PD. To further investigate the likely relation of these diseases, we have used a Drosophila PD model based on inactivation of the DJ-1β gene (ortholog of human DJ-1), and diet-induced Drosophila and mouse type 2 DM (T2DM) models, together with human neuron-like cells. T2DM models were obtained by feeding flies with a high sugar-containing medium, and mice with a high fat diet. Our results showed that both fly models exhibit common phenotypes such as alterations in carbohydrate homeostasis, mitochondrial dysfunction or motor defects, among others. In addition, we demonstrated that T2DM might be a risk factor of developing PD since our diet-induced fly and mouse T2DM models present DA neuron dysfunction, a hallmark of PD. We also confirmed that neurodegeneration is caused by increased glucose levels, which has detrimental effects in human neuron-like cells by triggering apoptosis and leading to cell death. Besides, the observed phenotypes were exacerbated in DJ-1β mutants cultured in the high sugar medium, indicating that DJ-1 might have a role in carbohydrate homeostasis. Finally, we have confirmed that metformin, an antidiabetic drug, is a potential candidate for PD treatment and that it could prevent PD onset in T2DM model flies. This result supports antidiabetic compounds as promising PD therapeutics.
ISSN: 1530-6860
DOI: 10.1096/fj.202200286R
Source: FASEB Journal [ISSN 0892-6638], v. 36 (8), e22432, (Agosto 2022)
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