Metabolic Dysfunction in Parkinson’s Disease: Unraveling the Glucose–Lipid Connection

Despite many years of research into the complex neurobiology of Parkinson’s disease, the precise aetiology cannot be pinpointed down to one causative agent but rather a multitude of mechanisms. Current treatment options can alleviate symptomsbut only slightly slow down the progression and not cure t...

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Main Authors: Jeswinder Sian-Hulsmann, Peter Riederer, Tanja Maria Michel
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/12/12/2841
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author Jeswinder Sian-Hulsmann
Peter Riederer
Tanja Maria Michel
author_facet Jeswinder Sian-Hulsmann
Peter Riederer
Tanja Maria Michel
author_sort Jeswinder Sian-Hulsmann
collection DOAJ
description Despite many years of research into the complex neurobiology of Parkinson’s disease, the precise aetiology cannot be pinpointed down to one causative agent but rather a multitude of mechanisms. Current treatment options can alleviate symptomsbut only slightly slow down the progression and not cure the disease and its underlying causes. Factors that play a role in causing the debilitating neurodegenerative psycho-motoric symptoms include genetic alterations, oxidative stress, neuroinflammation, general inflammation, neurotoxins, iron toxicity, environmental influences, and mitochondrial dysfunction. Recent findings suggest that the characteristic abnormal protein aggregation of alpha-synuclein and destruction of substantia nigra neurons might be due to mitochondrial dysfunction related to disturbances in lipid and glucose metabolism along with insulin resistance. The latter mechanism of action might be mediated by insulin receptor substrate docking to proteins that are involved in neuronal survival and signaling related to cell destruction. The increased risk of developing Type 2 Diabetes Mellitus endorses a connection between metabolic dysfunction and neurodegeneration. Here, we explore and highlight the potential role of glycolipid cellular insults in the pathophysiology of the disorder, opening up new promising avenues for the treatment of PD. Thus, antidiabetic drugs may be employed as neuromodulators to hinder the progression of the disorder.
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spelling doaj-art-41ebcef9d8704367af43078e7fb27a6c2025-08-20T02:53:23ZengMDPI AGBiomedicines2227-90592024-12-011212284110.3390/biomedicines12122841Metabolic Dysfunction in Parkinson’s Disease: Unraveling the Glucose–Lipid ConnectionJeswinder Sian-Hulsmann0Peter Riederer1Tanja Maria Michel2Department of Human Anatomy and Medical Physiology, University of Nairobi, P.O. Box 30197, Nairobi 00100, KenyaResearch Unit of Psychiatry, Department of Psychiatry, Odense, Region of Southern Denmark, University Hospital of Southern Denmark, 5000 Odense, DenmarkResearch Unit of Psychiatry, Department of Psychiatry, Odense, Region of Southern Denmark, University Hospital of Southern Denmark, 5000 Odense, DenmarkDespite many years of research into the complex neurobiology of Parkinson’s disease, the precise aetiology cannot be pinpointed down to one causative agent but rather a multitude of mechanisms. Current treatment options can alleviate symptomsbut only slightly slow down the progression and not cure the disease and its underlying causes. Factors that play a role in causing the debilitating neurodegenerative psycho-motoric symptoms include genetic alterations, oxidative stress, neuroinflammation, general inflammation, neurotoxins, iron toxicity, environmental influences, and mitochondrial dysfunction. Recent findings suggest that the characteristic abnormal protein aggregation of alpha-synuclein and destruction of substantia nigra neurons might be due to mitochondrial dysfunction related to disturbances in lipid and glucose metabolism along with insulin resistance. The latter mechanism of action might be mediated by insulin receptor substrate docking to proteins that are involved in neuronal survival and signaling related to cell destruction. The increased risk of developing Type 2 Diabetes Mellitus endorses a connection between metabolic dysfunction and neurodegeneration. Here, we explore and highlight the potential role of glycolipid cellular insults in the pathophysiology of the disorder, opening up new promising avenues for the treatment of PD. Thus, antidiabetic drugs may be employed as neuromodulators to hinder the progression of the disorder.https://www.mdpi.com/2227-9059/12/12/2841Parkinson’s diseasesubstantia nigraneurodegenerationglucose metabolismlipid metabolismmitochondria
spellingShingle Jeswinder Sian-Hulsmann
Peter Riederer
Tanja Maria Michel
Metabolic Dysfunction in Parkinson’s Disease: Unraveling the Glucose–Lipid Connection
Biomedicines
Parkinson’s disease
substantia nigra
neurodegeneration
glucose metabolism
lipid metabolism
mitochondria
title Metabolic Dysfunction in Parkinson’s Disease: Unraveling the Glucose–Lipid Connection
title_full Metabolic Dysfunction in Parkinson’s Disease: Unraveling the Glucose–Lipid Connection
title_fullStr Metabolic Dysfunction in Parkinson’s Disease: Unraveling the Glucose–Lipid Connection
title_full_unstemmed Metabolic Dysfunction in Parkinson’s Disease: Unraveling the Glucose–Lipid Connection
title_short Metabolic Dysfunction in Parkinson’s Disease: Unraveling the Glucose–Lipid Connection
title_sort metabolic dysfunction in parkinson s disease unraveling the glucose lipid connection
topic Parkinson’s disease
substantia nigra
neurodegeneration
glucose metabolism
lipid metabolism
mitochondria
url https://www.mdpi.com/2227-9059/12/12/2841
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AT peterriederer metabolicdysfunctioninparkinsonsdiseaseunravelingtheglucoselipidconnection
AT tanjamariamichel metabolicdysfunctioninparkinsonsdiseaseunravelingtheglucoselipidconnection