中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (7): 1437-1445.doi: 10.4103/1673-5374.387965

• 综述:退行性病与再生 • 上一篇    下一篇

重新思考神经退行性疾病:将脂质氧化与中枢神经系统疾病联系起来的神经代谢概念

  

  • 出版日期:2024-07-15 发布日期:2023-11-28

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

Steinunn Sara Helgudóttir1, #, Anne Skøttrup Mørkholt1, #, Jacek Lichota2, Preben Bruun-Nyzell1, Mads Christian Andersen2,  Nanna Marie Juhl Kristensen2, Amanda Krøger Johansen2, Mikela Reinholdt Zinn2, Hulda Maria Jensdóttir2,  John Dirk Vestergaard Nieland1, 2, *   

  1. 12N Pharma ApS, NOVI Science Park, Aalborg, Denmark; 2Molecular Pharmacology Group, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
  • Online:2024-07-15 Published:2023-11-28
  • Contact: John Dirk Vestergaard Nieland, PhD, jdn@hst.aau.dk.

摘要: https://orcid.org/0000-0001-7423-0122 (John Dirk Vestergaard Nieland) 

Abstract: 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.

Key words: brain disease, carnitine palmitoyl transferase 1, epigenetics, metabolism, gut microbiome, mitochondrial dysfunction, neurodegeneration, oxidative stress