Therapeutic Potential of Targeting Mitochondria for Alzheimer’s Disease Treatment
Abstract
:1. Introduction
2. The Mitochondrion: Its Dysfunctions in AD
2.1. Defective Mitochondrial Dynamics in AD
2.2. Defective Mitophagy in AD
2.3. Defective Mitochondrial Biogenesis in AD
2.4. Defective Mitochondrial Energy Metabolism in AD
3. Therapeutic Strategies Targeting Mitochondria for the Treatment of AD
3.1. Therapeutic Strategies Targeting Mitochondrial Bioenergetics
3.2. Therapeutic Strategies Targeting Mitochondrial Biogenesis
3.3. Therapeutic Strategies Targeting Mitochondrial Dynamics
3.4. Therapeutic Strategies Targeting Mitophagy
3.5. Therapeutic Strategies Targeting Mitochondria-Dependent Oxidative Damage
3.6. The Use of Nanoparticles Targeting Mitochondria in the Treatment of AD
- Most drugs do not cross the BBB [208,209]: this is why various efforts have been made to overcome the BBB. Apart from parenteral administration, according to which the drug would be injected directly into the spinal fluid [208], other methods involve chemical modification of the drug, the use of viruses/exosomes as vectors for the administration of the drug to the central nervous system [210,211], intranasal administration, in order to circumvent the obstacle of the BBB [208], the destruction of the BBB by ultrasound or radiotherapy [212] and finally, strategies based on nanotechnology.
- Selectively targeting drugs to mitochondria in vivo [208] needs to take into account the existence of a proton gradient (negative inner Δψm), which produces a strong negative potential on the IMM of approximately −160–180 mV [208] and influences the entry of the drug into the mitochondria, the presence of phospholipid cardiolipin and, last but not least, the impermeability of the mitochondria. If we add to all this the fact that four parts are distinguishable in the mitochondria, namely the MOM, the MIM, the intermembrane space (IMS) and the mitochondrial matrix, the task becomes very difficult. Both high and small molecular weight lipophilic particles (< and >500 mw) can freely penetrate through the MOM, but the Δψm makes the MIM resistant to anionic molecules [215]. Therefore, these barriers prevent the potential drug from being delivered to the mitochondrial space.
3.7. Intercellular Mitochondrial Transfer as Potential Therapeutic Approach for AD
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Atlante, A.; Amadoro, G.; Latina, V.; Valenti, D. Therapeutic Potential of Targeting Mitochondria for Alzheimer’s Disease Treatment. J. Clin. Med. 2022, 11, 6742. https://doi.org/10.3390/jcm11226742
Atlante A, Amadoro G, Latina V, Valenti D. Therapeutic Potential of Targeting Mitochondria for Alzheimer’s Disease Treatment. Journal of Clinical Medicine. 2022; 11(22):6742. https://doi.org/10.3390/jcm11226742
Chicago/Turabian StyleAtlante, Anna, Giuseppina Amadoro, Valentina Latina, and Daniela Valenti. 2022. "Therapeutic Potential of Targeting Mitochondria for Alzheimer’s Disease Treatment" Journal of Clinical Medicine 11, no. 22: 6742. https://doi.org/10.3390/jcm11226742
APA StyleAtlante, A., Amadoro, G., Latina, V., & Valenti, D. (2022). Therapeutic Potential of Targeting Mitochondria for Alzheimer’s Disease Treatment. Journal of Clinical Medicine, 11(22), 6742. https://doi.org/10.3390/jcm11226742