Protein Interactome of Amyloid-β as a Therapeutic Target
Abstract
1. Introduction
2. Aβ and Its Protein Interactors
2.1. Structural Features of Aβ
2.2. Protein Interactome of Aβ
2.3. Proteins Whose Function Is Affected by Aβ
2.3.1. Tau-Protein
2.3.2. α-Synuclein
2.4. Proteins Affecting Aβ Toxicity
2.4.1. Apolipoprotein E
2.4.2. Transthyretin
2.4.3. ABAD
2.4.4. GAPDH
2.4.5. Chaperones
2.4.6. Cystatin C
3. Chemicals Targeting Aβ and Its Intermolecular Complexes
Therapeutical Agent (Class of Agents) | Potential Function | Reference |
---|---|---|
Aducanumab (specific antibodies) and other agents preventing formation of Aβ fibrils formation | Prevention of Aβ assemblage into cytotoxic fibrils | [113] |
Synthetic and natural peptides that may block amyloid–amyloid binding | Interaction conditioned by the similarity to the hydrophobic domains of Aβ | [117] |
Small molecules able to inhibit Aβ misfolding and enhance its clearance (LS4, for example) | Specifically binding to different soluble forms of Aβ | [120] |
CPO-Aβ17–21 peptide | Blocking the ability of APOE to initiate Aβ oligomerization | [122] |
Cyclic peptide cG8 | TTR-mimetic peptide comprising its Aβ-binding domain | [124] |
Huperzine A and other ABAD blocking compounds | ABAD inhibition reduces Aβ-induced mitochondrial dysfunction | [127] |
GAPDH–Aβ complex inhibitors | Blocking the formation of the GAPDH–Aβ complex and reduction of its cytotoxicity | [94,138] |
Chaperone synthesis inducers | Newly synthesized chaperones block the formation of Aβ complexes with other proteins | [131,136,137] |
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Protein Name | Sample Source | Potential Function | Reference |
---|---|---|---|
Ubiquitin-activating enzyme E1 | Plaques | Ubiquitin-dependent proteosomal degradation of Aβ | [40] |
GFAP | Plaques | Activation of astrocytic immune response and astrocytic damage | [40] |
HSP70 | Extracellular vesicles | Involvement in ubiqitin-proteosomal and lysosomal degradation of Aβ, disaggregation of fibrils, and immune response activation | [41] |
PTGFRN | Extracellular vesicles | Positive regulation of APP procession and Aβ production | [46] |
GAPDH | Extracellular vesicles | Enhancement of Aβ aggregation and toxicity | [41] |
TTR | Extracellular vesicles | Blockage of Aβ nucleation | [41] |
CST3 | Extracellular vesicles | Negative regulation of Aβ oligomers and aggregate formation | [41] |
Tip60 | Protein–protein interaction | In complex with HDAC2 protection against AD-associated pathologies | [47] |
Fibulin 1 | Protein–protein interaction | Regulation of APP cleavage | [43] |
SLC25A4 | Protein–protein interaction | Unknown | [44] |
EME1 | Protein–protein interaction | Unknown | [45] |
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Lazarev, V.F.; Dutysheva, E.A.; Kanunikov, I.E.; Guzhova, I.V.; Margulis, B.A. Protein Interactome of Amyloid-β as a Therapeutic Target. Pharmaceuticals 2023, 16, 312. https://doi.org/10.3390/ph16020312
Lazarev VF, Dutysheva EA, Kanunikov IE, Guzhova IV, Margulis BA. Protein Interactome of Amyloid-β as a Therapeutic Target. Pharmaceuticals. 2023; 16(2):312. https://doi.org/10.3390/ph16020312
Chicago/Turabian StyleLazarev, Vladimir F., Elizaveta A. Dutysheva, Igor E. Kanunikov, Irina V. Guzhova, and Boris A. Margulis. 2023. "Protein Interactome of Amyloid-β as a Therapeutic Target" Pharmaceuticals 16, no. 2: 312. https://doi.org/10.3390/ph16020312
APA StyleLazarev, V. F., Dutysheva, E. A., Kanunikov, I. E., Guzhova, I. V., & Margulis, B. A. (2023). Protein Interactome of Amyloid-β as a Therapeutic Target. Pharmaceuticals, 16(2), 312. https://doi.org/10.3390/ph16020312