Diabetes Case Reports

Cross-talk between Iron overload and Glucose Metabolism in Neurodegeneration

7^th Annual Meeting on Diabetes and Endocrinology

November 18, 2024 | Webinar

Rosaria Ingrassia

University of Brescia, Italy

Scientific Tracks Abstracts: J Psychiatry

Abstract:

Significant neuroprotection was found by insulin and insulin-like growth factor 1 treatment during experimental cerebral ischemia, in acute ischemic stroke patients, in a rat 6-OHDA model of Parkinsonâ??s disease, and, interestingly, in clinical trials of Parkinsonâ??s patients treated with intranasal insulin which produced positive results in terms of both motor and cognitive symptoms. The involvement of Divalent metal transporter-1 (DMT1) and iron overload is already described in both ischemia and Parkinsonâ??s disease, particularly, DMT1 was recognized as a target gene of NF-kB in the early phase of post-ischemic neurodegeneration, both in vitro and in vivo, and not only the regulation of DMT1 by insulin has been previously described in Langerhans cells, but the Belgrade rat model of iron loading anemia, carrying a mutation of DMT1 that abrogates ferrous iron uptake, has normal metabolic response and pancreatic function, although with high serum iron concentrations. In this relationship, insulin controls the NFkB signaling and was shown to protect from ischemic cell death in rat cardiomyocytes. Furthermore, the protective role of insulin, which was demonstrated during in vitro ischemia in both mouse cortical neurons and differentiated human neuroblastoma cells, SK-N-SH, is associated with the downregulation of both DMT1 expression and ferrous iron-dependent cell death. We could indeed highlight the peculiar role of DMT1 as a pharmacological target, with the involvement of iron overload and ferroptosis in a reciprocal glucose neurodegeneration axis, recognized in several neurodegenerative diseases, where patients often develop diabetes, or vice versa, in diabetic patients that develop cerebrovascular diseases. Further studies are needed to increase the knowledge of the bidirectional relationship between metabolic impairment and neurodegeneration.received FDA approval for locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene aberrations. This review highlights the current clinical progress concerning the safety and efficacy of all the approved FGFR-TKIs (tyrosine kinase inhibitors) and their ongoing investigations in clinical trials for other oncogenic FGFR-driven malignancies.

Biography :

Rosaria Ingrassia, at the University of Brescia, has developed her expertise in iron overload and experimental mod els of neurodegeneration with attention to therapeutic strategies and molecular targeting. She could highlight a common molecular mechanism, with the contribution of epigenetic signaling, determining the upregulation of DMT1 expression and ferrous iron overload, involved in the early phase of several neurodegenerative diseases, like ischemia, in in vitro and in vivo models, mouse models of parkinsonisms, and primary fibroblasts of NBIA/BPAN affected patients, neurodegeneration with brain iron accumulation.