中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (1): 19-25.doi: 10.4103/1673-5374.224362

• 综述:退行性病与再生 • 上一篇    下一篇

调节线粒体生物能学可作为阿尔茨海默病的治疗策略

  

  • 收稿日期:2018-01-06 出版日期:2018-01-15 发布日期:2018-01-15

Modulation of mitochondrial bioenergetics as a therapeutic strategy in Alzheimer’s disease

Isaac G. Onyango   

  1. Gencia Biotechnology, Charlottesville, VA, USA
  • Received:2018-01-06 Online:2018-01-15 Published:2018-01-15
  • Contact: Isaac G. Onyang, DVM, Ph.D.,ionyango@genciabiotech.com.

Abstract:

 

Alzheimer’s disease (AD) is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved success in preclinical models addressing the pathological hallmarks of the disease, these efforts have not translated into any effective disease-modifying therapies. This could be because interventions are being tested too late in the disease process. While existing therapies provide symptomatic and clinical benefit, they do not fully address the molecular abnormalities that occur in AD neurons. The pathophysiology of AD is complex; mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress are antecedent and potentially play a causal role in the disease pathogenesis. Dysfunctional mitochondria accumulate from the combination of impaired mitophagy, which can also induce injurious inflammatory responses, and inadequate neuronal mitochondrial biogenesis. Altering the metabolic capacity of the brain by modulating/potentiating its mitochondrial bioenergetics may be a strategy for disease prevention and treatment. We present insights into the mechanisms of mitochondrial dysfunction in AD brain as well as an overview of emerging treatments with the potential to prevent, delay or reverse the neurodegenerative process by targeting mitochondria.

Key words: Alzheimer’s disease, mitochondria, bioenergetics, mitochondrial DNA, neuroinflammation, mitohormesis, caloric restriction, hypometabolism, mitophagy, mitochondrial biogenesis, recombinant-human mitochondrial transcription factor A, antioxidants, proteasome, mitochondrial transcription activator-like effector nucleases, clustered regularly interspaced short palindromic repeats/associated protein 9 (CRISPR/Cas9), caloric restriction, stem cells