P3 peptide

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Representation of the 3D structure of p3 peptide.[1]

p3 peptide also known as amyloid β- peptide (Aβ)17–40/42 is the

APP). It is known to be the major constituent of diffuse plaques observed in Alzheimer's disease (AD) brains and pre-amyloid plaques in people affected by Down syndrome. However, p3 peptide's role in these diseases is not truly known yet.[2]

Structure

There is little information related to the p3 peptides composition and structure, and moreover most of it has to do with characteristics that concern to its role in Alzheimer's disease. p3 can be found as a 24 or 26 residues peptide, depending on which is gamma secretase's cleavage. The peptide which has 26 residues, presents the following sequence:

  • VFFAEDVGSNKGAIIGLMVGGVVIAT[3]

In relation to the

hydrophobic core of the oligomers from being dissolved by the watered medium. So, p3 peptide oligomers would likely expose hydrophobic residues to water and would be less stable. As a consequence, p3 peptide structural determinants can assemble into fibrils, but no oligomeric forms have been identified. That is why p3 peptide represents the benign form of amyloid.[4]

Properties

Energy plays a very important role in p3 peptides. While

hydrophobic surfaces (60%) than Aβ oligomers do (20%), so buried surface areas are not as big within p3 oligomers (30%) as they are within Aβ oligomers. These evidences show that the expected energy of the Aβ-based oligomeric models of p3 is always positive and that these models expose hydrophobic patches to the solvent and bury a small proportion of their accessible surface within the oligomeric intermediates. Having these facts into account, we can state that p3 oligomers' existence is thermodynamically unfavourable, which suggests that the p3 peptide cannot form stable soluble oligomers in the same way Aβ does. Solution of p3 cannot assemble into stable oligomers as Aβ1–42 in the same concentration does. Therefore, it is very possible that p3 could not last long by itself, evolving rapidly into fibrillar forms that hide exposed hydrophobic patches.[4]

p3 peptides have been analyzed in some researches with Western blot techniques. Primary antibodies were used to recognize Aβ1–16 residues. Unexpectedly, it was discovered that the residues did not show any signal. This confirms the absence of N-terminal domain Aβ1-16 in p3 peptides.[4]

Synthesis

p3 peptide generates from the 17-40 or 17-42

Aβ respectively and releasing in both cases a cytoplasmic peptide fragment known as the APP intracellular domain (AICD). Both p3 and Aβ are sent to the extracellular medium.[4]

APP molecular processing and its different products. One of them is p3 peptide, which is sent to the extracellular medium.[1]

Role in Alzheimer’s disease and Down syndrome

p3 peptide is a product of non-amyloidogenic APP processing.

p3 peptide is known to have a role in AD and DS, however it has not been clearly determined yet.

In order to study the function of p3 peptide in AD, specific antibodies’ location techniques have been used to determine its absence or sparseness in aged non-AD brains. As it turns out, p3 peptide is prevalent in selected areas of AD brain in diffuse deposits and in a subset of dystrophic neuritis, both located in the temporal lobe limbic system.[5]

Although p3 peptide can assemble into

oligomeric forms. This might explain why p3 has no impact on synaptic function and therefore in AD, since it is a non-amyloidogenic product of APP.[4]

Despite this fact, p3 has been proved to have a role in formation of non-fibrillar deposits or lesions associated with DS, another

disorientation and deterioration of intellectual capacity.[2]

Since p3 has not been studied deeply, there are different opinions about its role in brain.

P3 peptides are thought to have a role in neuronal death and in the enhanced

inflammatory response in AD and DS, as it has been demonstrated that the treatment of cells with the p3 fragment, induced by the c-Jun N-terminal kinases (JNK) phosphorylation, is involved in neuronal cells apoptosis and causes the death of SH-SY5Y and IMR‐32 human neuroblastoma cells.[6]

References

  1. ^ a b PDB: 3MOQ​
  2. ^
    OCLC 315888712. Archived from the original on 2013-10-29. Retrieved 2013-10-22.[page needed
    ]
  3. ^ "Sequence Search: VFFAEDVGSNKGAIIGLMVGGVVIAT". Protein Data Bank.[permanent dead link]
  4. ^
    S2CID 43078358
    .
  5. PMID 8701997
    .
  6. PMID 12183349
    .

Further reading

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