Photodegradation of amyloid β and reduction of its cytotoxicity to PC12 cells using porphyrin derivatives

Abstract

A purpose-designed porphyrin-peptide hybrid effectively degraded amyloid β monomer and oligomers associated with Alzheimer's disease. Degradation was achieved using light irradiation in the absence of any additives and under neutral conditions. Moreover, the hybrid effectively neutralized the cytotoxicity of amyloid β in PC12 cells upon photoirradiation.

A Metalloporphyrin-Peptide Conjugate as an Effective Inhibitor of Amyloid-β Peptide Fibrillation and Cytotoxicity

“…In this respect, recent experimental work uses porphyrins and conjugates thereof as suppressors of β‐amyloid aggregation and cytotoxicity . Porphyrins have been used as pioneering agents not only for diagnostic imaging, but also for therapy .…”

“…Using a similar approach, Hirabayashy et al . were able to prevent the cytotoxic effects of Aβ42 in neuron‐like PC12 cells using a porphyrin‐peptide derivative in conjunction with photo‐irradiation to degrade Aβ42 monomer and oligomers …”

“…[17,18] In this respect, recent experimental work uses porphyrins and conjugates thereof as suppressors of b-amyloid aggregation and cytotoxicity. [19][20][21][22][23][24][25][26][27][28] Porphyrins have been used as 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 pioneering agents not only for diagnostic imaging, [22] but also for therapy. [23] Co-localization of deposits of heme in amyloid fibrils and some heme proteins within the senile plaques (SP) in AD brain, stimulated intensive investigation on heme-bound Ab complexes.…”

“…[26] Using a similar approach, Hirabayashy et al were able to prevent the cytotoxic effects of Ab42 in neuron-like PC12 cells using a porphyrin-peptide derivative in conjunction with photo-irradiation to degrade Ab42 monomer and oligomers. [27] In this paper we report the synthesis of a di-functional system consisting in a zinc-containing porphyrin moiety covalently linked to the GPGKLVFF peptide (1). In our mind, this new derivative would provide a new device to look inside the Ab's fibrillation process and a possible therapeutic approach.…”

Porphyrin–peptide conjugates in biomedical applications

“…Even though PDT has been mostly applied in the treatment of tumors, interesting results have been recently reported in degradation of amyloid β‐monomer and oligomers associated with Alzheimer's disease . Under photoirradiation the conjugate between a TPP derivative and the pentapeptide KLVFF, a key element in aggregation of 40‐ and 42‐residue amyloid β peptides, was more efficient to degrade oligomers than the porphyrin alone.…”