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