Latest Perspectives on Alzheimer’s Disease Treatment: The Role of Blood-Brain Barrier and Antioxidant-Based Drug Delivery Systems
Abstract
:1. Introduction
2. Molecular Mechanism of Alzheimer’s Disease
2.1. Amyloid-Beta and Tau Dynamics
2.2. Chronic Inflammation in Alzheimer’s Disease
2.3. Impact of Oxidative Stress in Alzheimer’s Disease
2.4. Role of Insulin Resistance in Alzheimer’s Disease
2.5. Association between Alzheimer’s Disease and Gut Microbiota
3. The Role of Blood-Brain-Barrier in the Pathophysiology of Alzheimer’s Disease
3.1. Physiology of the BBB
3.2. Transport Mechanisms across the Blood-Brain Barrier
3.2.1. Carrier-Mediated Transport
3.2.2. Receptor-Mediated Transport
3.2.3. Active Transport
3.2.4. Passive Diffusion
3.3. Disruption of Blood-Brain Barrier in Alzheimer’s Disease
3.3.1. Permeability of the Blood-Brain Barrier in Alzheimer’s Disease
3.3.2. Neuroinflammation in Alzheimer’s Disease
3.3.3. Amyloid-β Deposition and Blood-Brain Barrier Dysfunction
4. Drug Delivery Systems with Antioxidant Molecules for Targeting the Treatment of Alzheimer’s Disease
4.1. Impact of Natural Antioxidant Molecules in AD Treatment
4.1.1. Curcumin
4.1.2. Quercetin
4.1.3. Phytol
4.1.4. Carotenoids
4.1.5. Resveratrol
4.1.6. Hesperetin
4.1.7. Ginsenosides
4.2. Overview of Nanoparticle-Based Drug Delivery Systems
4.2.1. Polymeric Nanoparticles
4.2.2. Dendrimers
4.2.3. Lipid-Based Nanoparticles
4.2.4. Inorganic NPs
4.2.5. Nanoemulsions
5. Discussion
5.1. Strengths and Weaknesses of Different Antioxidant-Based Approaches
5.2. Patient Outcomes and Therapeutic Strategies
5.3. Challenges and Future Perspectives
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Antioxidant | Nanoparticle (NP) Type | Targeted Pathway | Mechanism of Action | Advantages | References |
---|---|---|---|---|---|
Curcumin | PEG-PLA NPs (<80 nm) | - | - |
| [69] |
PLGA NPs modified with Tet1 (150–200 nm) | Oxidative stress response | DPPH radical scavenging activity |
| [67] | |
PLGA-PEG NPs modified with B6 (<100 nm) | - | - |
| [66] | |
Se NPs loaded with curcumin/PLGA composites (160 ± 5 nm) | Amyloidogenic pathway | - |
| [68] | |
Silica NPs (60 nm) | - | - |
| [92] | |
Quercetin | PLGA NPs (<145 nm) | Amyloidogenic pathway | - |
| [72] |
Concave cubic AuPd NPs modified with PS-80 (71 nm) | Autophagy-lysosomal pathway | - |
| [73] | |
Lipid NPs (SLC and NLC) modified with transferrin (200 nm) | Amyloidogenic pathway | - |
| [93] | |
Lipid NPs (SLC and NLC) modified with RVG29 (<250 nm) | Amyloidogenic pathway | - |
| [94] | |
Se NPs modified with acacia and PS-80 (89.90 ± 4.17 nm) | Oxidative stress response | DPPH radical scavenging activity |
| [95] | |
Sulfur NPs inserted into microbubbles (<100 nm) | Oxidative stress response | Reduce ER stress and reduce oxidative stress caused by ER stress or eliminate ROS |
| [96] | |
MSNPs modified with PEG3k (200–250 nm) | Amyloidogenic pathway | - |
| [4] | |
Exosomes NPs (40–150 nm) | Tau phosphorylation | Inhibit CDK5-mediated tau phosphorylation |
| [97] | |
SPIONs (30–50 nm) | Oxidative stress response | Enhance expression levels of antioxidant enzymes and reduces expression of NO synthetase |
| [98] | |
Resveratrol | SLNs modified with OX26 mAb and containing grape seed extract (254 ± 17 nm) | Amyloidogenic pathway | - |
| [99] |
SeNPs (<100 nm) | Amyloidogenic pathway | SeNPs have a strong affinity for Aβ42 plaques |
| [83] | |
Nanostructured hydrogel (132 ± 11.90 nm) | - | - |
| [84] | |
Gold NPs (<100 nm) | - | - |
| [85] | |
RBC coated NLC with RVG29 and TPP (<160 nm) | Mitochondrial oxidative stress response | Specifically bind to neurons and target the mitochondria |
| [100] | |
Selenium/Chitosan NPs (19.93 ± 1.52 nm) | Modulating gut microbiota | Restoring gut microbiota |
| [101] | |
Phytol | PLGA NPs (177.4 ± 5.9 nm) | Mitochondrial oxidative stress response | Stabilizing the mitochondrial membrane |
| [75,76] |
Fucoxanthin | PLGA-PEG NPs (<210 nm) | Amyloidogenic pathway | Enhance antioxidant enzyme activity and reduce neuroinflammation |
| [79] |
Lutein | Chitosan/PLGA SNPs (<150 nm) | Oxidative stress response | Scavenging ROS species |
| [81] |
Astaxanthin | SSLNs (< 200 nm) | - | - |
| [102] |
Liposomal PEG NPs (<80 nm) | Amyloidogenic pathway | Scavenging formaldehyde |
| [80] | |
Thymoquinone | Nanoemulsion | Amyloidogenic pathway | Modulating APP processing |
| [103] |
PLGA NPs modified with PS80 (<230 nm) | Oxidative stress response | Reducing superoxide radical production |
| [104] | |
Ginsenoside Rg3 | PLGA NPs modified with angiopep-2 (100 nm) | Amyloidogenic pathway | Downregulation of AβPP-A4 expression levels |
| [105] |
Hesperetin | Nanosuspension | Oxidative stress response | Upregulation of antioxidant enzyme genes |
| [106] |
Nanocrystals | Oxidative stress response | - |
| [107] | |
Nanocrystals (170–800 nm) | - | - |
| [89] | |
Huperzine A | PLGA NPs modified with Lf and TMC (<154 nm) | - | - |
| [108] |
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Daraban, B.S.; Popa, A.S.; Stan, M.S. Latest Perspectives on Alzheimer’s Disease Treatment: The Role of Blood-Brain Barrier and Antioxidant-Based Drug Delivery Systems. Molecules 2024, 29, 4056. https://doi.org/10.3390/molecules29174056
Daraban BS, Popa AS, Stan MS. Latest Perspectives on Alzheimer’s Disease Treatment: The Role of Blood-Brain Barrier and Antioxidant-Based Drug Delivery Systems. Molecules. 2024; 29(17):4056. https://doi.org/10.3390/molecules29174056
Chicago/Turabian StyleDaraban, Bianca Sânziana, Andrei Sabin Popa, and Miruna S. Stan. 2024. "Latest Perspectives on Alzheimer’s Disease Treatment: The Role of Blood-Brain Barrier and Antioxidant-Based Drug Delivery Systems" Molecules 29, no. 17: 4056. https://doi.org/10.3390/molecules29174056