title: A Novel Way of Amelioration of Amyloid Beta Induced Toxicity inCaenorhabditis elegans.
abstract: BACKGROUND
  With an incidence of 1 in 85 persons above the age of 60 years succumbing to the disease, Alzheimer's disease (AD), has been predicted to create havoc globally. In spite of enormous efforts and exhaustive research, no cure is in sight. Hence, it is critical to unravel the mechanism of AD development/protection and identification of a cure soon.
  
  
  OBJECTIVE
  This study is aimed at investigating the mechanism of reserpine action, which alleviates the toxicity of amyloid beta (Aβ) (AD-causing peptide) inCaenorhabditis elegans[1, 2].
  
  
  METHODS
  Determination of alleviation of Aβ toxicity with reserpine manifested as reduction in progressive paralysis, in the background of GFP reporter driven by the promoter of the FMRFamide neuropeptide, FLP-11 (AD; Pflp-11::GFP) and acetylcholine contribution through aldicarb (which inhibits acetylcholine esterase) treatment.
  
  
  RESULTS
  The most significant protection against Aβ toxicity was obtained in the background of Pflp-11::GFP. This protection had 2 components. The promoter of FLP-11 with the reporter GFP, Pflp-11::GFP, per se gave significant protection. Further reserpine treatment provided additional alleviation. Together they could almost eliminate Aβ toxicity. These 2 components of Aβ toxicity alleviation are dependent on acetylcholine levels, as an increase in acetylcholine by aldicarb treatment reduces the protective effect.
  
  
  CONCLUSIONS
  A unique way to alleviate Aβ toxicity is reserpine treatment in combination with Pflp-11::GFP. Reserpine should be evaluated as a potential drug in a pilot study in AD patients. Furthermore, identification of the mechanism of Pflp-11::GFP-mediated reduction in Aβ toxicity is a potential pathway to develop therapeutics for AD.
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, India; Department of Bioscience and Biotechnology, Banasthali University, Banasthali Vidyapith, India.
authors.forename: Kopal
authors.initials: K
authors.lastname: Saharia
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, India.
authors.forename: Ranjeet
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, India.
authors.forename: Kuldeep
authors.initials: K
authors.lastname: Gupta
authors.affiliation: Department of Bioscience and Biotechnology, Banasthali University, Banasthali Vidyapith, India.
authors.forename: Shrilekha
authors.initials: S
authors.lastname: Mishra
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, India; Center for Preclinical and Translational Medicine Research, Central Research Facility, Sri Ramachandra University, Chennai, India.
authors.forename: Jamuna R
authors.initials: JR
authors.lastname: Subramaniam
keywords: Acetylcholine; Alzheimer disease; Amyloid beta; FLP-11; Neuropeptide