CN-121991178-A - Synthetic peptides, pharmaceutical compositions comprising the same and use of the same for the treatment of amyloid degenerative diseases

Abstract

The invention provides a synthetic peptide, a pharmaceutical composition containing the synthetic peptide and application of the synthetic peptide in treating amyloid degeneration diseases. The synthetic peptide of the invention achieves the effect of treating amyloid degeneration diseases through various efficacy experiments.

Inventors

• ZHOU DEYANG
• QIU SHAOZHI
• HUANG SHIWEI
• PAN ZHIMING
• CHEN MEIZHI
• LIN YUQUAN
• CHEN YE
• WU ZHONGJUN

Assignees

• 台湾“中国医药大学附设医院”

Dates

Publication Date

20260508

Application Date

20250617

Priority Date

20241104

Claims (14)

1. 1. A synthetic peptide comprises an amino acid sequence as shown in SEQ ID NO. 1.
2. 2. The synthetic peptide of claim 1, which targets β -amyloid β (aβ).
3. 3. The synthetic peptide of claim 2, which prevents the formation of β -amyloid aggregates.
4. 4. The synthetic peptide of claim 3, which prevents aggregation of the whole amyloid β sheet.
5. 5. The synthetic peptide of claim 4, wherein the whole amyloid protein is β -amyloid (aβ), tau protein, α -synuclein (α -Syn), islet amyloid protein (IAPP), or transthyretin (TTR).
6. 6. The synthetic peptide of claim 5, wherein the Tau protein is a recombinant Tau P301L protein.
7. 7. The synthetic peptide of claim 5, wherein the TTR is recombinant TTR V122I.
8. 8. The synthetic peptide of claim 5, wherein the TTR is recombinant TTR V30I.
9. 9. The synthetic peptide of claim 1 which maintains 1-methyl-4-phenylpyridine (MPP) + -treated SH-SY 5Y-derived dopaminergic neuron cell activity.
10. 10. The synthetic peptide of claim 1, which prevents the formation of amyloid aggregates in MPP + -treated SH-SY 5Y-derived dopaminergic neurons.
11. 11. The synthetic peptide of claim 1, which prevents the formation of amyloid aggregates in aβ -treated SH-SY 5Y-derived neuronal-like cells.
12. 12. A pharmaceutical composition comprising the synthetic peptide of any one of claims 1 to 11 and a pharmaceutically acceptable carrier.
13. 13. Use of a synthetic peptide according to any one of claims 1 to 11 for the preparation of a medicament for the treatment of an amyloidogenic disease.
14. 14. The use according to claim 13, wherein the amyloidosis disease is parkinson's disease or alzheimer's disease.

Description

Synthetic peptides, pharmaceutical compositions comprising the same and use of the same for the treatment of amyloid degenerative diseases Technical Field The present invention relates to a synthetic peptide, a pharmaceutical composition comprising the synthetic peptide and the use of the synthetic peptide for the treatment of amyloidogenic diseases. Background Amyloid (amyloid) is an insoluble fibrous protein. Abnormal accumulation in organs can cause amyloidogenic disease (amyloidosis). In many neurological diseases, such as Alzheimer's Disease (AD), parkinson's Disease (PD), the occurrence of a large number of accumulated deposits of amyloid in the nervous system can be observed. Many scholars believe that it may lead to degeneration or dysfunction of the brain or other organs. Alzheimer's Disease (AD) is characterized by the accumulation of beta-amyloid (Abeta) in the brain, which is a major cause of mental retardation worldwide, affecting an increasing population of the elderly. According to the international alzheimer's association report, more than 5 million people worldwide had developing mental retardation in 2020, and the number was doubled almost every 20 years, with 8,200 tens of thousands being reached in 2030 and 1.52 million more at 2050. Unfortunately, most types of dyszhia are currently incurable. If a valuable teaching is drawn from the failure of a large number of clinical trials of new drugs for Alzheimer's disease, it is the intervention of early treatment should be taken when the deposition and entanglement of amyloid beta (Abeta) has not yet caused irreversible damage to the brain. In view of the disadvantages of side effects, chemical synthesis and insignificant effects of the current drugs for treating amyloid degeneration diseases. In order to solve the above problems, there is a need for developing new and more effective pharmaceuticals for treating amyloidosis diseases to facilitate a broad population of such needs. Disclosure of Invention Accordingly, the present invention provides a synthetic peptide comprising an amino acid sequence shown in SEQ ID NO. 1. In one embodiment of the invention, the synthetic peptide targets β -amyloid β (aβ). In one embodiment of the invention, the synthetic peptide prevents the formation of beta-amyloid aggregates. In one embodiment of the invention, the synthetic peptide prevents aggregation of the whole amyloid β sheet. In one embodiment of the invention, the whole amyloid is β -amyloid (aβ), tau protein, α -synuclein (α -Syn), islet amyloid (Islet amyloid polypeptide, IAPP) or transthyretin (TRANSTHYRETIN, TTR). In one embodiment of the invention, the Tau protein is a recombinant Tau P301L protein. In one embodiment of the invention, the TTR is a recombinant TTR V122I. In one embodiment of the invention, the TTR is a recombinant TTR V30I. In one embodiment of the invention, the synthetic peptide maintains 1-methyl-4-phenylpyridine(MPP) + -treated SH-SY 5Y-derived dopaminergic neuron cell activity. In one embodiment of the invention, the synthetic peptide prevents the formation of amyloid aggregates in MPP + -treated SH-SY 5Y-derived dopaminergic neurons. In one embodiment of the invention, the synthetic peptide prevents the formation of amyloid aggregates in aβ -treated SH-SY 5Y-derived neuronal-like cells. It is another object of the present invention to provide a pharmaceutical composition comprising a synthetic peptide as described above and a pharmaceutically acceptable carrier. It is another object of the present invention to provide the use of a synthetic peptide as described above for the preparation of a medicament for the treatment of an amyloidogenic disease (amyloidosis). In one embodiment of the invention, the amyloid-modifying disease is Parkinson's Disease (PD) or Alzheimer's Disease (AD). In summary, the present invention achieves the efficacy of treating amyloidogenic diseases (e.g., parkinson's disease and alzheimer's disease) by the results exemplified in the examples below. The following examples are given for the purpose of illustration only and are not intended to limit the scope of the invention, since various changes and modifications may be made therein by one skilled in the art without departing from the spirit and scope of the invention as defined in the following claims. Drawings FIG. 1 shows the affinity of PAA peptides for Tau fibrils. Fig. 2 shows that PAA peptides can prevent aggregation of the whole amyloid β sheet (aβ). Figure 3 shows that PAA peptides can prevent aggregation of the whole amyloid β sheet (Tau). FIG. 4 shows that the PAA peptide prevents aggregation of the Tau protein (P301L). Fig. 5 shows that PAA peptides can prevent aggregation of the whole amyloid β sheet (α -Syn). Fig. 6 shows that PAA peptides can prevent aggregation of the whole amyloid β sheet (IAPP). Fig. 7 shows that PAA peptide prevents aggregation of whole amyloid β sheet (TTR V122I). Fig. 8 shows that PAA peptide prevents aggregatio