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Restoring autophagic function: a case for type 2 diabetes mellitus drug repurposing in Parkinson's disease.

ABSTRACT: Parkinson's disease (PD) is a predominantly idiopathic pathological condition characterized by protein aggregation phenomena, whose main component is alpha-synuclein. Although the main risk factor is ageing, numerous evidence points to the role of type 2 diabetes mellitus (T2DM) as an etiological factor. Systemic alterations classically associated with T2DM like insulin resistance and hyperglycemia modify biological processes such as autophagy and mitochondrial homeostasis. High glucose levels also compromise protein stability through the formation of advanced glycation end products, promoting protein aggregation processes. The ability of antidiabetic drugs to act on pathways impaired in both T2DM and PD suggests that they may represent a useful tool to counteract the neurodegeneration process. Several clinical studies now in advanced stages are looking for confirmation in this regard.

SUBMITTER: Greco M

PROVIDER: S-EPMC10654753 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Restoring autophagic function: a case for type 2 diabetes mellitus drug repurposing in Parkinson's disease.

Greco Marco M Munir Anas A Musarò Debora D Coppola Chiara C Maffia Michele M

Frontiers in neuroscience 20231103

Parkinson's disease (PD) is a predominantly idiopathic pathological condition characterized by protein aggregation phenomena, whose main component is alpha-synuclein. Although the main risk factor is ageing, numerous evidence points to the role of type 2 diabetes mellitus (T2DM) as an etiological factor. Systemic alterations classically associated with T2DM like insulin resistance and hyperglycemia modify biological processes such as autophagy and mitochondrial homeostasis. High glucose levels a ...[more]

PMID: 38027497

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| S-EPMC9147745 | biostudies-literature

Drug-repurposing identified the combination of Trolox C and Cytisine for the treatment of type 2 diabetes.

Project description:BACKGROUND: Drug-induced gene expression dataset (for example Connectivity Map, CMap) represent a valuable resource for drug-repurposing, a class of methods for identifying novel indications for approved drugs. Recently, CMap-based methods have successfully applied to identifying drugs for a number of diseases. However, currently few gene expression based methods are available for the repurposing of combined drugs. Increasing evidence has shown that the combination of drugs may valid for novel indications. METHOD: Here, for this purpose, we presented a simple CMap-based scoring system to predict novel indications for the combination of two drugs. We then confirmed the effectiveness of the predicted drug combination in an animal model of type 2 diabetes. RESULTS: We applied the presented scoring system to type 2 diabetes and identified a candidate combination of two drugs, Trolox C and Cytisine. Finally, we confirmed that the predicted combined drugs are effective for the treatment of type 2 diabetes. CONCLUSION: The presented scoring system represents one novel method for drug repurposing, which would provide helps for greatly extended the space of drugs.

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