Diabetes as a risk factor for neurodegenerative diseases

master's thesis

• Title (croatian): Dijabetes kao rizik za razvoj neurodegenerativnih bolesti
• Author: Laura Tomić
• Mentor: Jelena Osmanović Barilar (mentor)
• Committee member: Jelena Osmanović Barilar (predsjednik povjerenstva)
• Committee member: Ana Hladnik (član povjerenstva)
• Committee member: Jasenka Markeljević (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pharmacology); Zagreb
• Defense date and country: 2020-07-17, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Pharmacology

Abstract

Both diabetes mellitus and neurodegenerative diseases have become major health challenges worldwide. Diabetes mellitus is now known to be a major risk factor for cognitive decline, dementia and Parkinson’s disease. It has also been shown that the risk of cognitive decline and neurodegeneration is not only seen in diabetic patients, but it is also increased in patients with prediabetes and metabolic syndrome. Chronic hyperglycemia suppresses substantia nigra dopaminergic neuronal firing and decreases dopamine turnover, as well as induces chronic brain insulin resistance, ultimately leading to impaired brain insulin signaling. Recent studies have focused on the role of insulin and impaired insulin signaling as a link between diabetes and neurodegenerative diseases. Impairments in brain insulin signaling mechanisms, together with hyperglycemia, might induce the molecular and biochemical changes such as dysfunction of the mitochondria, oxidative damage, and inflammatory responses, ultimately leading to pathological lesions seen in neurodegenerative diseases, as well as in diabetes mellitus. In addition, microvascular changes are also a critical factor involved in the etiology of diabetes mellitus and neurodegenerative diseases. Taken together, the complex systemic effects of diabetes mellitus on neurodegenerative diseases require further investigation.

Abstract (croatian)

Šećerna bolest i neurodegenerativne bolesti postale su velikim zdravstvenim izazovima današnjice. Šećerna bolest poznata je kao glavni faktor rizika za kognitivne poremećaje, demencije i Parkinsonovu bolest. Rizik za razvoj neurodegenerativnih bolesti i kognitivnih poremećaja nije samo povećan kod šećerne bolesti, već i kod pacijenata s predijabetesom ili metaboličkim sindromom. Kronična hiperglikemija potiskuje “paljenje” dopaminergičkih neurona substantije nigre i smanjuje omjer dopamina i njegovih metabolita, te inducira kroničnu inzulinsku rezistenciju u mozgu i dovodi do promijenjene signalizacije inzulina u mozgu. Nedavne studije usmjerene su na ulogu inzulina i promijenjenu signalizaciju inzulina kao poveznicu između dijabetesa i neurodegenerativnih bolesti. Oštećenja u mehanizmima signalizacije inzulina u mozgu, zajedno s hiperglikemijom, mogu izazvati molekularne i biokemijske promjene kao što su disfunkcija mitohondrija, oksidativni stres, i upalni odgovori, što u konačnici dovodi do patoloških lezija u neurodegenerativnim bolestima, kao i do šećerne bolesti. Osim navedenih promjena, mikrovaskularne promjene ključni su čimbenik u etiologiji šećerne bolesti i neurodegenerativnih bolesti. Stoga, s obzirom na vrlo kompleksnu pozadinu ovih procesa, složeni sistemski učinci šećerne bolesti na razvoj neurodegenerativnih bolesti zahtijevaju daljnje istraživanje.

• Keywords: diabetes; neurodegenerative diseases; Alzheimer’s; Parkinson’s
• Keywords (croatian): šećerna bolest; neurodegenerativne bolesti; Alzheimer; Parkinson
• Language: english
• URN:NBN: urn:nbn:hr:105:074921
• Study programme: Title: Medicine (in English language); Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-10-15 11:00:00