Neural Regeneration Research (Jan 2024)

Rethinking neurodegenerative diseases: neurometabolic concept linking lipid oxidation to diseases in the central nervous system

  • Steinunn Sara Helgudóttir,
  • Anne Skøttrup Mørkholt,
  • Jacek Lichota,
  • Preben Bruun-Nyzell,
  • Mads Christian Andersen,
  • Nanna Marie Juhl Kristensen,
  • Amanda Krøger Johansen,
  • Mikela Reinholdt Zinn,
  • Hulda Maria Jensdóttir,
  • John Dirk Vestergaard Nieland

DOI
https://doi.org/10.4103/1673-5374.387965
Journal volume & issue
Vol. 19, no. 7
pp. 1437 – 1445

Abstract

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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.

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