TY - JOUR
T1 - Rethinking neurodegenerative diseases
T2 - neurometabolic concept linking lipid oxidation to diseases in the central nervous system
AU - Helgudóttir, Steinunn Sara
AU - Mørkholt, Anne Skøttrup
AU - Lichota, Jacek
AU - Bruun-Nyzell, Preben
AU - Andersen, Mads Christian
AU - Kristensen, Nanna Marie Juhl
AU - Johansen, Amanda Krøger
AU - Zinn, Mikela Reinholdt
AU - Jensdóttir, Hulda Maria
AU - Nieland, John Dirk Vestergaard
N1 - Copyright © 2024 Copyright: © 2024 Neural Regeneration Research.
PY - 2024/7/1
Y1 - 2024/7/1
N2 - Currently, there is a lack of effective medicines capable of halting or reversing the progression of neurodegenerative disorders, including amyotrophic lateral sclerosis, Parkinson's disease, multiple sclerosis, or Alzheimer's disease. Given the unmet medical need, it is necessary to reevaluate the existing paradigms of how to target these diseases. When considering neurodegenerative diseases from a systemic neurometabolic perspective, it becomes possible to explain the shared pathological features. This innovative approach presented in this paper draws upon extensive research conducted by the authors and researchers worldwide. In this review, we highlight the importance of metabolic mitochondrial dysfunction in the context of neurodegenerative diseases. We provide an overview of the risk factors associated with developing neurodegenerative disorders, including genetic, epigenetic, and environmental factors. Additionally, we examine pathological mechanisms implicated in these diseases such as oxidative stress, accumulation of misfolded proteins, inflammation, demyelination, death of neurons, insulin resistance, dysbiosis, and neurotransmitter disturbances. Finally, we outline a proposal for the restoration of mitochondrial metabolism, a crucial aspect that may hold the key to facilitating curative therapeutic interventions for neurodegenerative disorders in forthcoming advancements.
AB - Currently, there is a lack of effective medicines capable of halting or reversing the progression of neurodegenerative disorders, including amyotrophic lateral sclerosis, Parkinson's disease, multiple sclerosis, or Alzheimer's disease. Given the unmet medical need, it is necessary to reevaluate the existing paradigms of how to target these diseases. When considering neurodegenerative diseases from a systemic neurometabolic perspective, it becomes possible to explain the shared pathological features. This innovative approach presented in this paper draws upon extensive research conducted by the authors and researchers worldwide. In this review, we highlight the importance of metabolic mitochondrial dysfunction in the context of neurodegenerative diseases. We provide an overview of the risk factors associated with developing neurodegenerative disorders, including genetic, epigenetic, and environmental factors. Additionally, we examine pathological mechanisms implicated in these diseases such as oxidative stress, accumulation of misfolded proteins, inflammation, demyelination, death of neurons, insulin resistance, dysbiosis, and neurotransmitter disturbances. Finally, we outline a proposal for the restoration of mitochondrial metabolism, a crucial aspect that may hold the key to facilitating curative therapeutic interventions for neurodegenerative disorders in forthcoming advancements.
KW - brain disease
KW - carnitine palmitoyl transferase 1
KW - epigenetics
KW - gut microbiome
KW - metabolism
KW - mitochondrial dysfunction
KW - neurodegeneration
KW - oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=85180333120&partnerID=8YFLogxK
U2 - 10.4103/1673-5374.387965
DO - 10.4103/1673-5374.387965
M3 - Review article
C2 - 38051885
SN - 1673-5374
VL - 19
SP - 1437
EP - 1445
JO - Neural Regeneration Research
JF - Neural Regeneration Research
IS - 7
ER -