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Lipopolysaccharide from Gut Microbiota Modulates α-Synuclein Aggregation and Alters Its Biological Function.

Abstract：

:Altered intestinal permeability has been correlated with Parkinson's pathophysiology in the enteric nervous system, before manifestations in the central nervous system (CNS). The inflammatory endotoxin or lipopolysaccharide (LPS) released by gut bacteria is known to modulate α-synuclein amyloidogenesis through the formation of intermediate nucleating species. Here, biophysical techniques in conjunction with microscopic images revealed the molecular interaction between lipopolysaccharide and α-synuclein that induce rapid nucleation events. This heteromolecular interaction stabilizes the α-helical intermediates in the α-synuclein aggregation pathway. Multitude NMR studies probed the residues involved in the LPS-binding structural motif that modulates the nucleating forms, affecting the cellular internalization and associated cytotoxicity. Collectively, our data characterizes this heteromolecular interaction associated with an alternative pathway in Parkinson's disease progression.

journal_name

ACS Chem Neurosci

journal_title

ACS chemical neuroscience

authors

Bhattacharyya D,Mohite GM,Krishnamoorthy J,Gayen N,Mehra S,Navalkar A,Kotler SA,Ratha BN,Ghosh A,Kumar R,Garai K,Mandal AK,Maji SK,Bhunia A

doi

10.1021/acschemneuro.8b00733

subject

Has Abstract

pub_date

2019-05-15 00:00:00

pages

2229-2236

issue

5

issn

1948-7193

journal_volume

10

pub_type

杂志文章

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