Polyamines and its analogue modulates amyloid fibrillation in lysozyme: A comparative investigation.
BACKGROUND
Polyamines can induce protein aggregation that can be related to the physiology of the cellular function. Polyamines have been implicated in protein aggregation which may lead to neuropathic and non neuropathic amyloidosis.


SCOPE OF REVIEW
Change in the level of polyamine concentration has been associated with ageing and neurodegeneration such as Parkinson's disease, Alzheimer's disease. Lysozyme aggregation in the presence of polyamines leads to non neuropathic amyloidosis. Polyamine analogues can suppress or inhibit protein aggregation suggesting their efficacy against amyloidogenic protein aggregates.


MAJOR CONCLUSIONS
In this study we report the comparative interactions of lysozyme with the polyamine analogue, 1-naphthyl acetyl spermine in comparison with the biogenic polyamines through spectroscopy, calorimetry, imaging and docking techniques. The findings revealed that the affinity of binding varied as spermidine > 1-naphthyl acetyl spermine > spermine. The biogenic polyamines accelerated the rate of fibrillation significantly, whereas the analogue inhibited the rate of fibrillation to a considerable extent. The polyamines bind near the catalytic diad residues viz. Glu35 and Asp52, and in close proximity of Trp62 residue. However, the analogue showed dual nature of interaction where its alkyl amine region bind in same way as the biogenic polyamines bind to the catalytic site, while the naphthyl group makes hydrophobic contacts with Trp62 and Trp63, thereby suggesting its direct influence on fibrillation.


GENERAL SIGNIFICANCE
This study, thus, potentiates, the development of a polyamine analogue that can perform as an effective inhibitor targeted towards aggregation of amyloidogenic proteins.
['Kabir|Ayesha|A|', 'Jash|Chandrima|C|', 'Payghan|Pavan V|PV|', 'Ghoshal|Nanda|N|', 'Kumar|Gopinatha Suresh|GS|']
D000682:Amyloid D000686:Amyloidosis D000818:Animals D030161:Avian Proteins D015317:Biogenic Polyamines D002645:Chickens D057927:Hydrophobic and Hydrophilic Interactions D062105:Molecular Docking Simulation D009113:Muramidase D066329:Protein Aggregates D066263:Protein Aggregation, Pathological D013095:Spermidine D013096:Spermine
Polyamine Lysozyme Protein aggregation Amyloidosis 1-napthyl acetyl spermine (NASPM) Atomic force microscopy Neurodegenerative diseases