Journal
ACTA PHARMACEUTICA SINICA B
Volume 12, Issue 6, Pages 2778-2789Publisher
INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2022.03.001
Keywords
Neurodegenerative diseases; Mitochondria; Targeting drug; Apoptosis; Reactive oxygen species; Adenosine triphosphate; Mitochondrial membrane potential; Evaluation
Categories
Funding
- National Key R&D Program of China [2020YFA0709900]
- National Natural Science Foundation of China [22077101]
- China-Sweden Joint Mobility Project (China) [51811530018]
- Postdoctoral Research Funding Schemes of Jiangsu Province (China)
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Neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, are characterized by progressive degeneration of neurons. Dysfunction of mitochondria is believed to be the underlying cause of these diseases, making mitochondria a preferred target for intervention. While some mitochondria-targeting drugs have shown promising outcomes, there are still obstacles that hinder their development.
Neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD) and Parkinson's disease (PD) are a heterogeneous group of disorders characterized by progressive degeneration of neurons. NDDs threaten the lives of millions of people worldwide and regretfully remain incurable. It is well accepted that dysfunction of mitochondria underlies the pathogenesis of NDDs. Dysfunction of mitochondria results in energy depletion, oxidative stress, calcium overloading, caspases activation, which dominates the neuronal death of NDDs. Therefore, mitochondria are the preferred target for intervention of NDDs. So far various mitochondria-targeting drugs have been developed and delightfully some of them demonstrate promising outcome, though there are still some obstacles such as targeting specificity, delivery capacity hindering the drugs development. In present review, we will elaborately address 1) the strategy to design mitochondria targeting drugs, 2) the rescue mechanism of respective mitochondria targeting drugs, 3) how to evaluate the therapeutic effect. Hopefully this review will provide comprehensive knowledge for understanding how to develop more effective drugs for the treatment of NDDs. (C)2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
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