Abstract
Hyperglycemia is one of the major risk factors responsible for memory impairment in diabetes which may lead to Alzheimer’s disease (AD) at a later stage. MicroRNAs are a class of non-coding RNAs that are found to play a role in diabetes. Downregulation of microRNA-29b in diabetes is well reported. Moreover, microRNA-29b is also reported to target the 3′ UTR of β-secretase (BACE-1) enzyme which is involved in the formation of amyloid-beta (Aβ) in AD via cleavage of amyloid precursor protein (APP). Therefore, the present study was designed to elucidate whether microRNA-29b could be a link between diabetes and dementia. In the in vitro and in vivo diabetic model, we found downregulation of microRNA-29b due to hyperglycemia. After human microRNA-29b treatment, there was a significant improvement in the short-term and spatial memory in diabetic mice. Also, the human microRNA-29b treatment decreased oxidative stress and BACE-1 activity in diabetes. The present findings revealed that the downregulation of microRNA-29b in diabetes could be associated with memory impairment and increased BACE-1 activity. These results would give a future direction to study the role played by microRNAs in diabetes-associated memory impairment and hence aid in the development of therapeutics to treat the same.
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The research was carried out at National Institute of Pharmaceutical Education and Research-Ahmedabad with the financial aid from Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Government of India.
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Kavya Jash: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software and Writing—Original draft. Piyush Gondaliya: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software and Writing—Original draft. Aditya Sunkaria: Conceptualization, Supervision, Writing—Review & Editing. Kiran Kalia: Project administration, Resources, Supervision.
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Jash, K., Gondaliya, P., Sunkaria, A. et al. MicroRNA-29b Modulates β-Secretase Activity in SH-SY5Y Cell Line and Diabetic Mouse Brain. Cell Mol Neurobiol 40, 1367–1381 (2020). https://doi.org/10.1007/s10571-020-00823-4
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DOI: https://doi.org/10.1007/s10571-020-00823-4