Human insulin modulates α-synuclein aggregation via DAF-2/DAF-16 signalling pathway by antagonising DAF-2 receptor in C. elegans model of Parkinson's disease.

Content Provider	Europe PMC
Author	Haque, Rizwanul Shamsuzzama Kumar, Lalit Sharma, Tanuj Fatima, Soobiya Jadiya, Pooja Siddiqi, Mohammad I. Nazir, Aamir
Abstract	Insulin-signalling is an important pathway in multiple cellular functions and organismal ageing across the taxa. A strong association of insulin-signalling with Parkinson’s disease (PD) has been proposed but the exact nature of molecular events and genetic associations are yet to be understood. We employed transgenic C. elegans strain harboring human α-synuclein::YFP transgene, towards studying the aggregation pattern of α-synuclein, a PD-associated endpoint, under human insulin (Huminsulin®) treatment and DAF-16/DAF-2 knockdown conditions, independently and in combination. The aggregation was increased when DAF-16 was knocked-down independently or alongwith a co-treatment of Human insulin (HumINS) and decreased when DAF-2 was knocked-down independently or alongwith a co-treatment of HumINS; whereas HumINS treatment per se, reduced the aggregation. Our results depicted that HumINS decreases α-synuclein aggregation via DAF-2/DAF-16 pathway by acting as an antagonist for DAF-2 receptor. Knockdown of reported DAF-2 agonist (INS-6) and antagonists (INS-17 and INS-18) also resulted in a similar effect on α-synuclein aggregation. Further by utilizing bioinformatics tools, we compared the differences between the binding sites of probable agonists and antagonists on DAF-2 including HumINS. Our results suggest that HumINS treatment and DAF-16 expression play a protective role against α-synuclein aggregation and its associated effects.
Journal	Oncotarget
Volume Number	11
PubMed Central reference number	PMC7021237
Issue Number	6
PubMed reference number	32110282
e-ISSN	19492553
DOI	10.18632/oncotarget.27366
Language	English
Publisher	Impact Journals LLC
Publisher Date	2020-02-11
Access Restriction	Open
Rights License	Copyright: Haque et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Subject Keyword	Parkinson’s human insulin aggregation Daf-2 Caenorhabditis elegans (C. elegans)
Content Type	Text
Resource Type	Article
Subject	Oncology